d o c to r a l m w w m se r ie s

uni CiCUC lA/UAT/fflS M TNMtllb

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AUTHOR

fCMb tftU A SOUMttt

UNIVERSITY.
DEGREE

HO!' STATE CPU,

PLD.

d a te

PUBLICATION NO.

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CYCLIC V A R I A T I O N S

IN THYROID FUNCTION OF MATURE

FEM ALE

RATS AND MICE

By
FOUAD

ATALLA SOLIMAN

A THESIS
Subm itted to t H e S c h o ol o> G ra d u a te Studies o: Michigan
State C o l l e g e of A g r ic u ltu r e and Applied Science
in p a r t i a l f u h i l i m e n t of the r e q u i r e m e n t s
f or the d e g re e o~

DOCTOR

D ep artm en t

OF PHILOSOPHY

of Physiology and Pharmacology

1952

CYCLIC

VARIATIONS IN THYROID F U N C T I O N O F
FEM ALE

MATURE

RATS AND MICE

By
F o u a d A talla Solim an

AN A B S T R A C T
S u b m i t t e d to t h e S c h o o l of G r a d u a t e S t u d i e s of M ic h i g a n
St a t e C o l l e g e of A g r i c u l t u r e a n d A p p l i e d S c ie n c e
in p a r t i a l f u l f i l l m e n t of the r e q u i r e m e n t s
f o r the d e g r e e of

D O C T O R O F P H IL O S O P H Y

D e p a r t m e n t of P h y s i o l o g y and P h a r m a c o l o g y

Year

1952

1
FOUAD

ATALLA

A series
of t h e f a c t o r s
pitu itary ,

1.

ABSTRACT

of e x p e r i m e n t s

w a s p e r f o r m e d to d e t e r m i n e

i n v o l v e d in t h e h o r m o n a l b a l a n c e of the t h y r o i d ,

D eterm inations

w ere

and body w e ig h ts

m a d e of o x y g e n c o n s u m p t i o n body

of r a t s

u n d e r b a s a l conditions

cycle.

It w a s fou nd t h a t t h e r e

s t a g e s of t h e e s t r o u s

sig n ifican tly in c r e a s e d oxygen co n su m p tio n during e s t r u s .
w ere

some

and o v ary .

tem perature
the f o u r

SO L IM A N

during
is a

There

no s i g n i f i c a n t d i f f e r e n c e s b e t w e e n b a s a l t e m p e r a t u r e s o r

body w eights

2.
of r a t s

a t th e f o u r

The

stages

of th e e s t r o u s

s t u d y of r a d i o i o d i n e u p ta k e by the t h y r o i d gl a n d s

d u r in g the e s t r o u s

cycle

showed that th e r e

i n c r e a s e d uptake during e s t r u s .
at m etestru s

cycle.

and a tta in s

is a s i g n i f i c a n t l y

The u p ta k e g r a d u a l l y d e c r e a s e s

it s l o w e s t l e v e l d u r i n g d i e s t r u s

a nd p r o -

e stru s.

3.

S im ilar

g l a n d s of m i c e
lic

s t u d i e s of r a d i o i o d i n e u p ta k e by the t h y r o i d

d u r i n g t he e s t r o u s

v ariatio n different fro m

of r a d i o i o d i n e

cycle

t h a t of th e

sh o w e d a p a t t e r n of c y c ­
rat.

The m a x i m a l upta ke

i s a t t a i n e d by the t h y r o i d s of p r o e s t r o u s m i c e .

2
F O U A D A T A L L A SO L IM A N

4.

A s i n g le i n j e c tion of

b e n z o a t e i n c r e a s e d the s i x - h o u r

ABSTRACT

s ix o r 300 r a t - u n i t s

of

uptake of r a d i o i o d i n e

h o u r s a f t e r the e s t r o g e n injection.

T h e r e w e r e no

estrad io l

fo rty -eig h t

d iffe ren c e s

b e tw e en the e f f e c t s of the two d o s e s on t h y r o i d u p t a k e f w i t h the
c o n c lu sio n t h a t the d o s e of ei tr o g e n is not v e r y

5.

c ritic a l.

The p r o l o n g e d a d m i n i s t r a t i o n of a l a r g e

gen did n o t c h an ge the r ad ioiodine uptake by the

dose

of e s t r o ­

th y ro id s

when

c o m p a r e d to c o n t r o l s .

6.

A s in g le d o s e of 0.2

o r 0.4 m i l l i g r a m o f

d e c r e a s e d the uptake of radioiodine
of 0 .8 m i l l i g r a m

7.

p ro g estero n e

by the t h y r o i d s

w h ile

a dose

i n c r e a s e d the uptake.

The i n j e c t i o n of 0.4 m i l l i g r a m of p r o g e s t e r o n e

t e r a c t e d the e f f e c t of e s t r o g e n on thyr oid f u n c tio n

w ith

coun­

the n e t

r e s u l t of a d e c r e a s e d ra dioiodine uptake.

8.
rats

Experiments

with h y p o p h y s e c t o m i z e J - o v a r i e c t o m i z e d

showed that e strogen produces

its

stimulating

thyroid gland via the pituitary gland since

effect

it did n o t

on

change

the
the

radioiodine uptake in such animals.

A

3
FOUAD A TA LLA

SO L IM A N

9.

ABSTRACT

P rogesterone

d e c r e a s e d the u p tak e of r a d i o i o d i n e

t h e t h y r o i d g l a n d s of h y p o p h y s e c t o m i z e d

rats

sh ow ing t h a t i t d o e s

n o t in d u c e i t s e f f e c t m a i n l y v i a the p i t u i t a r y .

10.
of e s t r o u s

The th y r o tr o p h ic
rats

is

s l i g h t l y h i g h e r th a n t h a t of r a t s

s t a g e s of t h e e s t r o u s
of t h e b l o o d s e r u m
a t the o t h e r t h r e e

The
form ation

h o r m o n e p o t e n c y of the p i t u i t a r i e s

cycle.

a t the o t h e r

The t h y r o t r o p h i c h o r m o n e

of e s t r o u s

rats

exceeds

content

s l i g h t l y t h a t of r a t s

s t a g e s of the c y c l e .

r e s u l t s of the p r e s e n t i n v e s t i g a t i o n s t o g e t h e r w i t h i n ­
reported e a rlie r,

e s t a b l i s h e d c l e a r l y the f a c t t h a t t h e r e

is a r e c i p r o c a l b a l a n c e b e t w e e n the h o r m o n e s of the t h y r o i d g l a n d
a n d the o v a r y .

This b a la n c e

i s m e d i a t e d in p a r t v ia the p i t u i t a r y

a n d in p a r t v i a o t h e r p a t h w a y s .
In e x p e r i m e n t a l a n i m a l s
of f o l l i c l e

stim ulating horm one

hypothyroidism favors

w h ile, h y p e r t h y r o i d i s m f a v o r s

p r o d u c t i o n s of l u t e n i z i n g h o r m o n e .
m ore

the p r o d u c t i o n

In the

a c t i v e p r i o r to a n d d u r i n g o v u la tio n .

the

r a t the t h y r o i d g l a n d i s
It b e c o m e s l e s s

active

d u r in g the l u t e a l d e v e l o p m e n t a n d a l s o d u r in g the g r a a f i a n f o l l i c l e
developm ent.

4
FOUAD

A T A L L A

Such
the

o v a ria n

w hile

SO L IM A N

cy clic

p itu ita r y .

v a r i a t i o n of thy ro id a c tiv ity is c o n t r o l l e d by

horm ones.

p r o g e s te rone

ABSTRACT

E s t r o g e n a c tiv a te s it via the p i t u i t a r y ,

d e p r e s s e s it throug h o t h e r pa thw a ys than the

To
m y father,
A ta lla Solim an

ACKNOW LEDGM ENTS

I sh o u l d l i k e to e x p r e s s m y

s i n c e r e g r a t i t u d e f o r the h e l p ,

g u i d an c e , an d e n c o u r a g e m e n t g i v e n m e by D r . E . P .
P r o f e s s o r of P h y s i o l o g y ,

M ic h i g a n S ta te C o lle g e .

R e in e k e ,

D r . B. V.

A l f r e d s o n , H e a d of t h e D e p a r t m e n t oi P h y s i o l o g y and P h a r m a c o l o g y ,
w a s v e r y g e n e r o u s i n p r o v i d in g the l a b o r a t o r y f a c i l i t i e s oi the d e ­
partm ent.

Dr.

L.

F.

W oiterink,

D r.

J o s e p h M e i t e s , a n d D r.

C o l lin g s w e r e v e r y h e l p f u l with t h e i r v a lu a b le
t ha n k s a r e

e x t e n d e d to M r s .

E llen F.

Feng, M r. W a lla c e F r i e d b e r g ,

M r.

suggestions.

W. D.
My

Monkus, M i s s Yu Sheng L.

W i ll ia m P .

B a k e r , and M r.

R o b e r t L. C o r n w a l l f o r t h e i r t e c h n i c a l a s s i s t a n c e and v a lu a b l e

sug­

gestions .
I appreciate

t h e a s s i s t a n c e oi M r.

J. M o n r o e in c a r i n g f o r

the a n i m a l s .
F i n a l l y , m y d e e p a p p r e c i a t i o n i s e x te n d e d to the E g y p t i a n
G o v e rn m e n t f o r th e o p p o rtu n ity affo rd ed m e
ship that m a d e th is w o rk p o s s ib le .

th r o u g h the s c h o l a r ­

TABLE

OF

CONTENTS

Page
I N T R O D U C T I O N ..........................................................................................................

1

REVIEW O F L I T E R A T U R E

3

.........................................

T h y ro id a l and M etabolic R hythm s
i n th e F e m a l e
..........................

3

T h y r o i d H i s t o l o g y .......................................................................................

3

B a s a l M etabolic Rate

...........................................................................

4

..........................................................................................................

4

D o g s .................................................................................................................

6

R a t s ............................................................................

7

Wo m e n

B a s a l B o d y T e m p e r a t u r e ....................................................................
Women

7

.......................................... ' .............................................................

7

R a t s .................................................................................................................

10

T h e I n f lu e n c e of A l t e r a t i o n s i n T h y r o i d
A c ti v i ty on R e p r o d u c t i o n ...........................................................................
H ypothyroidism

II

..........................................................................................

II

M e n s t r u a l c y c l e ..................................................................................

11

E strous

12

cycle

......................................................................................

R e s p o n s e to g o n a d o t r o p h i n s ..........................

15

P i t u i t a r y g o n a d o t r o p h i n ................................................................

16

V

Page
G estation

..................................................................................................

16

H y p e r t h y r o i d i s m ...........................................................................................

17

H o r m o n a l I n t e r r e l a t i o n s h i p s ....................................................................

22

E f f e c t o f T h y r o i d on R e s p o n s e to E s t r o g e n ...................

22

Iodine d is tr ib u tio n

............................................................................

T h y ro id-pituitary relationship

23

..............................................

24

.........................................................

29

T h e e f f e c t s of c a s t r a t i o n of f e m a l e
a n i m a l s on t h y r o i d a c t i v i t y .....................................................

29

T h e e f f e c t s of e s t r o g e n i c c o m p o u n d s
on t h y r o i d a c t i v i t y ............................................................................

32

M e t a b o l i c e f f e c t s of e s t r o g e n .................................................

35

T h e e f f e c t s of p r o g e s t e r o n e on the
t h y r o i d .........................................................................................................

36

O v a r y - A d r e n a l R e l a t i o n s h i p ............................................................

38

T h y r o i d - A d r e n a l R e l a t i o n s h i p ........................................................

42

T hyroid O vary R elationships

T h e e f f e c t s of t h e t h y r o i d gla nd on
the a d r e n a l s
................................................

42

T h e e f f e c t s of s t r e s s

on t h y r o i d a c t i v i t y ...................

44

T h e e f f e c t s of th e a d r e n a l c o r t e x and ACTH
on t h y r o i d a c t i v i t y a s s tu d ie d by r a d i o a c t i v e
i o d i n e .............................................................................................................

46

vi
Page
E x p e r i m e n t I:
Oxygen C o n su m p tio n , B a s a l
T e m p e r a t u r e s , a n d Bo d y W e i g h t s of F e m a l e
R a t s a s C o r r e l a t e d w i t h t h e S t a g e s of the
E s t r o u s C y c l e ......................................................................................................
M a t e r i a l s and M ethod s

53

........................................................................

53

..................................................................................................

55

R e s u l t s .................................................................................................................

56

B o d y w e i g h t s ..........................................................................................

56

B asal tem perature

...........................................................................

56

.......................................................................

56

E x p e r i m e n t 11: 1*31 U p t a k e by the T h y r o i d
G l an d of F e m a l e R a t s a t th e S t a g e s of the
E s t r o u s C y c l e ......................................................................................................

59

C alculations

O x yg e n c o n s u m p t i o n

M a t e r i a l s and M eth ods

.......................................................................

59

R e s u l t s .................................................................................................................

61

1*31 U p t a k e ..............................................................................................

61

T h e w e i g h t s of o r g a n s

................................................................

63

E x p e r i m e n t III:
1*81 U p ta k e by the T h y r o id
G la n d of F e m a l e R a t s G e t t i n g S t a n d a r d Nal
In t a k e a t th e S t a g e s of t h e E s t r o u s C y c l e ..............................

66

M a t e r i a l s a nd M e t h o d s

.......................................................................

66

R e s u l t s ................................................................................................................

68

1^^

uptake

.............................................................................................

T h e w e i g h t s of o r g a n s

...............................................................

68
68

vii
Page
E x p e r i m e n t s IV (A) a n d (B):
11^1 U ptake by
th e T h y r o i d G l a n d of F e m a l e M ic e a t the
S t a g e s of t h e E s t r o u s C y c le
................................................................

72

........................................................................

72

R e s u l t s .................................................................................................................

73

M a t e r i a l s and M eth ods

l!31

Up t a k e

..............................................................................................

73

B o d y w e i g h t s a n d t h y r o i d w e i g h t s ......................................

74

E x p e r i m e n t V:
Th e E f f e c t s of E s t r o g e n and
P r o g e s t e r o n e on 1*^* Uptake by the T h y r o id
G la n d of O v a r i e c t o m i z e d R a t s
............................................................

77

M aterials

and M ethods

.......................................................................

R e s u l t s .............................
131 u p t a k e

77
79

..............................................................................................

79

........................................................

83

E x p e r i m e n t VI:
T h e E f f e c t of E s t r o g e n on
1131 U p tak e b y th e T h y r o i d G l a n d s of
O v a r i e c t o m i z e d and O v a r i e c t o m i z e d ,
A d re n a lec to m iz e d Rats
...............................................................................

84

1

B od y a n d t h y r o i d w e ig h ts

M a t e r i a l s and M ethods

.......................................................................

84

R e s u l t s ................................................................................................................

86

1

131 u p t a k e

Body weights

.............................................................................................
........................................................

86
91

T h y r o i d w e i g h t s ..................................................................................

94

P i t u i t a r y w eights

95

..............................................................................

viii
Page
A d r e n a l w e i g h t s ...................................................................................
E x p e r i m e n t VII:
The* E f f e c t s of E s t r o g e n
a nd P r o g e s t e r o n e on 1131 U p tak e by the
T h y r o i d G l a n d s of H y p o p h y s e c t o m i z e d O v a r ie c to m iz e d and O v a r ie c to m iz e d R a ts

95

..............................

97

........................................................................

97

R e s u l t s .................................................................................................................

99

..............................................................................................

99

M a te r ia ls and M ethods

I 131 u p t a k e

Bo d y w e i g h t s ................................................................................................
T h y r o i d w e i g h t s ...................................................................................
P itu ita r y w eights

100
103

.....................................................................................

103

A d r e n a l w e i g h t s ........................................................................................

103

E x p e r i m e n t VIII:
T hyrotrophic Horm one P o ­
t e n c y of t he P i t u i t a r i e s a nd P l a s m a of R a t s
a t th e S t a g e s of t h e E s t r o u s C y c l e .......................................................

104

M a t e r i a l s and M eth o d s

.............................................................................

104

R e s u l t s ......................................................................................................................

105

D I S C U S S I O N ..........................................................................................................................

H°

BIBLI OG RA PHY

.............................................................................

IN T R O D U C T IO N

The

st u d y of d u c t l e s s g l a n d s and the

s e c r e t i o n s a n d f u n c t i o n s h a v e c h a l l e n g e d the
n u m b e r of i n v e s t i g a t o r s .

s i g n i f i c a n c e of t h e i r
interests

of a l a r g e

I t i s a f ie ld in w hich th e d a n g e r of i n ­

a c c u r a t e l y p la n n e d o r c o n t r o l l e d e x p e r i m e n t s i s u n u s u a l l y g r e a t .
T his is tr u e

wh e n s t u d y i n g the i n t e r r e l a t i o n s h i p b e t w e e n the t h y ­

r o i d an d r e p r o d u c t i o n in t h e f e m a l e .
Several factors,

s u c h a s t h e d o s e of h o r m o n e , the

species

o r e n v i r o n m e n t , a n d d i f f e r e n c e s i n e x p e r i m e n t a l c o n d it io n s , m i g h t
be r e s p o n s i b l e f o r d i s a g r e e m e n t b e t w e e n the s e v e r a l i n v e s t i g a t o r s
i n t h is f ie l d .
The
larger

e a r l y a n a t o m i s t s n o t i c e d that the

in wom en than in m e n .

Freund

th y r o i d gla nd is

(1883) n o t i c e d a l s o

that

the t h y r o i d e n l a r g e s i n w o m e n d u r i n g m e n s t r u a l p e r i o d s and p r e g ­
n a n cy .

C l i n i c a l i n v e s t i g a t i o n s p o in t out the i m p o r t a n c e of a n o r m a l

t h y r o i d f o r w o m e n to a t t a i n n o r m a l

se x fu n c tio n s.

M any c l i n i c a l

o b s e r v a t i o n s h a v e b e e n r e p o r t e d on m e n s t r u a l d i s t u r b a n c e s d u r i n g
the c o u r s e of t h y r o i d d i s e a s e s , u s u a l l y a m e n o r r h e a ^ o r i r r e g u l a r i t y
of the o n s e t of m e n s e s .

T h e r e i s no doubt, then, th a t a h o r m o n a l i n t e r r e l a t i o n s h i p
e x i s ts b etw een the o v a r i e s and the t h y r o i d .

S o f a r , th e r e is no

evidence of the s p e c i f ic m e c h a n i s m s i n v o l v e d .
O u r in v e s t i g a t i o n s a r e a i m e d a t p r e s e n t i n g

a c l e a r e r picture

of t h y r o i d - o v a r i a n r e l a t i o n s h i p s in two s p e c ! c s s of a n i m a l s :
and the m o u s e .

The f i r s t s t ep was (1) to

f in d

if t h e r e a r e d i f f e r ­

e nc e s in oxygen c o n s u m p t i o n and b a s a l t e m p e r a t u r e
during the f o u r s t a g e s of the e s t r o u s c y c l e .

of the e s t r o u s c y c l e .

Our aim also w as

a tion in th y r o i d a c t i v i t y follows the s a m e

in ic e
to

f i n d if the cyclic v a r i ­

le d

a l s o the ef f e c t s of e s t r o g e n and p r o g e s t e r o n e
in p h y sio l o g ic a l d o s e s .

In o th e r w o r d s , w o

iodine by the

a t the four s t a g e s

p a tte rn

The r e s u l t s f r o m t h e s e e x p e r i m e n t s

of fem al e r a t s

a n d (2) to d e te r m i n e

if t h e r e a r e d i f f e r e n c e s in the uptake of r a d i o a c t i v e
thyroid g lan ds of m a t u r e f e m a le r a t s a n d

the r a t

in both s p e c i e s .

us to inv es t i ga t e

given to spayed r a t s

t r i e d to duplicate a s

c l o se l y a s p o s s i b l e the n o r m a l p h y s i o l o g i c s a . 1

cond itions.

We w e r e a l s o i n t e r e s t e d in d e t e r m i n i n g

the ro le of both the

a d r e n a l s and p i t u i t a r y i n c o ntro lling o r m o d i f y i n g

t h y r o id - o v a r i a n

responses.
T he l a s t s t e p i n o u r w ork was to a s s a y
cy of the r a t p i t u i t a r i e s and blood d u r i n g

tlie

the th y ro tro p i c p o t e n ­
fo ur s ta g e s of the c ycle.

RE VI EW O F

LITERATURE

T h y r o i d a l a n d M e t a b o l i c R h y t h m s in the F e m a l e

T h y r o i d H is t o lo g y

H i s t o l o g i c a l s t u d i e s of the th y r o i d gland a t the v a r i o u s
s t a g e s of t he c y c l e h a v e

s h o w n t h a t in young r a t s

the m i t o t i c

a c t i v it y of th e t h y r o i d and p i t u i t a r y i n c r e a s e d s o m e w h a t in e a r l y
e s t r u s and r e a c h e d a m a x i m a l a c t i v i t y in both d i e s t r u s
estrus, as

r e p o r t e d by H u n t (1944).

and p r o -

Since the g r e a t e s t m i t o t i c

a c t i v i t y of the t h y r o i d a n d h y p o p h y s i s o c c u r s in both g la n d s d u r i n g
l a t e e s t r u s , i t m i g h t be a s s u m e d t h a t a si n g le f a c t o r i s
for t h e ir activ ity .

responsible

Hunt stated that such stim ulating effect a p p e a r s

f i r s t in the t h y r o i d a n d n o t in the p i t u i t a r y - - t h a t i s , d u rin g e a r l y
estrus.

T herefore,

t h e m i t o s i s - s t i m u l a t i n g f a c t o r is not n e c e s s a r ­

il y the s a m e f o r b o t h g l a n d s .
H istological

s t u d i e s of the pig e o n th y r o i d show ed th a t t h i s

o r g a n i s i n a s t a t e of h y p e r a c t i v i t y d u r in g f o l l i c u l a r g ro w th a s o b ­
s e r v e d by M a r z a a n d B l i n o v (1936).
In a n o t h e r

species,

n a m e l y the g u in e a pig, Chouke et a l.

(1935) r e p o r t e d t h a t the m i n i m a l m i t o t i c a c t i v i t y of the t h y r o i d

4
c o r r e s p o n d s to th e f o l l i c u l a r p h a s e ( e s t r u s ) and t h a t m a x i m a l
a c t i v it y c o r r e s p o n d s to th e lu t e a l p h a s e ( d i e s t r u s ) .

A s i m i l a r re *

l a t i o n sh i p w a s n o t i c e d i n w o m e n w h e r e Bing (1928) r e p o r t e d m a x ­
i m a l m i t o t i c a c t i v i t y c o r r e s p o n d i n g to the m e n s t r u a t i o n p e r i o d .

B a s a l M e ta b o lic R a te

W omen.

S e v e r a l w o r k e r s have m e a s u r e d the m e t a b o l i c

r a t e in the w o m a n d u r i n g the m e n s t r u a l c y c le.
considerably.

Some i n v e s t i g a t o r s

Their resu lts vary

c o n c lud e d th a t t h e r e w e r e no

d e m o n s t r a b l e d i f f e r e n c e s b e t w e e n the b a s a l m e t a b o l i c

rate m e a ­

s u r e m e n t s e i t h e r d u r i n g the m e n s t r u a l o r i n t e r m e n s t r u a l p e r i o d s
( G e p h a r t and Du B o i s ,

1916; B lunt and Dye,

1921; an d L a n z ,

1924).

B lu n t a n d Dye found a d e c r e a s e of 1.6 p e r c e n t in the b a s a l
m etabolic

r a t e d u r i n g m e n s t r u a t i o n , but they po inted out t h a t v a r i ­

a t i o n s of th is m a g n i t u d e m a y o c c u r a t an y t im e without a p p a r e n t
causes.
However, th e re

s e e m s to be s o m e a g r e e m e n t t h a t t h e r e i s a

r i s e i n the m e t a b o l i c r a t e d u r in g the w e e k p r e c e d i n g the o n s e t of
m e n s t r u a t i o n a s i n d i c a t e d by Rowe and E a k in (1921), a n d W a k e h a m s
(1923).

5
C o n k l in a n d C l e n d o n (1930) found t h a t the b a s a l m e t a b o l i c
ra t _

te n d s to r e a c h i t s

l o w e s t le v e l following m e n s t r u a t i o n a n d i t s

hig hest level p re c e d in g m e n s t r u a t i o n .
with C o n k li n a n d Cl e n d o n .

G r i f f i t h ejt al.

(1929) a g r e e d

T h e y a d d e d t h a t t h e r e i s no s i g n i f i c a n t

c o r r e l a t i o n b e t w e e n the i n t r a - i n d i v i d u a l v a r i a t i o n s

of body t e m p e r ­

a t u r e an d m e t a b o l i s m .
Kunde (1923) r e p o r t e d t h a t t h e r e i s a d e c r e a s e in m e t a b o l i c
r a t e d u r i n g the l i r s t o r

s e c o n d day of m e n s t r u a t i o n .

and C o l l e t (1924) r e p o r t e d t h a t the b a s a l m e t a b o l i c
the f i r s t o r
perio d.
rise,

is low on

r e p o r t e d th a t t h e r e i s f r e q u e n t l y a p r e m e n s t r u a l

an d a s e c o n d low p o i n t in the m e t a b o l i c

m i d d l e of the i n t e r m e n s t r u a l p e r i o d .
and lo w l e v e l s

rate

the m e t a b o l i c

r a t e o c c u r s a t the

The d i f f e r e n c e b e tw e e n high

a m o u n t s to 5 p e r c e n t .

H it c h c o c k a n d W a r d w e ll (1929), f r o m
in t w e n t y w o m e n ,
rate

v.hich o c c u r s

t h e i r stud y on the b a s a l

r e p o r t e d a s t r o n g te n d e n c y f o r

to be l o w e r e d d u r in g the m e n s t r u a l p e r i o d .

T he y a l s o iound t h a t t h e r e i s a n o t h e r
rate

rate

s e c o n d d ay of m e n s t r u a t i o n and often th r o u g h o u t the

They a U o

m etabolic

H afkesbring

low po int in the m e t a b o l i c

a b o u t th e m i d d l e of the i n t e r m e n s t r u a l p e r i o d .

O ther investig ators

reporting

and F i n n (1928) a nd M c C l e n d o n e_t a l.

sim ilar
(1929).

results

w ere Benedic t

6
Dogs.

Kunde e t a l .

norm al b asal m etabolic
T he b a s a l m e t a b o l i c
s u b c u t a n e o u s l y wi th

(1930) r e p o r t e d th a t t h e r e i s a low

r a t e i n the dog d u r i n g

r a t e in n o r m a l o r c a s t r a t e
100 o r 200 r a t - u n i t s

spontaneous e s t r u s .
d o gs when i n j e c t e d

of e s t r i n d u r i n g a p e r i o d

of t en to t h i r t y d a y s w a s o n ly 2 p e r c e n t b e lo w the a v e r a g e of
the c o n t r o l s .

R ats.
fem ale

Lee

(1927) d e t e r m i n e d the b a s a l m e t a b o l i c

r a t s a t th e

d i f f e r e n t s t a g e s o£ the e s t r o u s

that heat production p e r
average in c re a se

square m e te r

c y c le .

of s u r f a c e a r e a

r a t e of
He found

sho w ed an

of 12 p e r c e n t i n the l a s t te n h o u r s of d i e s t r u s

a n d a t t h e b e g i n n i n g of p r o e s t r u s .
O variectom ized ra ts

The R. Q. w a s c o n s t a n t a t 0.75

s h o w e d a n a v e r a g e d e c r e a s e in t h e i r h e a t p r o

d u c t i o n of 10 p e r c e n t b e l o w the d e t e r m i n a t i o n s m a d e b e f o r e the
r e m o v a l of t he o v a r i e s .
Wang (1923,

1924) a n d S l o n a k e r (1925) n o t i c e d t h a t in the

r a t the e s t r u s p h a s e

i s a c c o m p a n i e d by a p r o n o u n c e d i n c r e a s e

lo c o m o to r activ ity and an i n c r e a s e
B r o b e c k e t a I.

in e n e r g y e x p e n d i t u r e .

(1947) found th a t food in ta k e d u ri n g d i e s t r u s

e x c e e d e d th e i n t a k e d u r i n g e s t r u s by a s m u c h a s
day.

in

6 gram s per

He w e n t l u r t h e r to s a y th a t food in ta k e c h a n g e s w e r e m o r e

r e g u l a r t h a n the v a r i a t i o n s in a c t i v i t y ; in fact, the m a g n i t u d e of

7
the c h a n g e s i n food i n t a k e a n d t h e i r

r e g u la r ity sug gests that a

r e c o r d of food c o n s u m p t i o n m i g h t s e r v e a s a n a c c e p t a b l e c r i t e r i o n
of t h e s e x c y c l e of t he r a t .

T his is

t r u e only if r a t s a r e

a constant env iro n m en tal t e m p e r a tu r e .

E strous

kept a t

r a ts lost fro m

10

to 12 g r a m s i n th e i n d i v i d u a l c y c l e s due to d e c r e a s e of food i n t a k e
a nd i n c r e a s e d e x p e n d i t u r e of e n e r g y .

B a s a l Body T e m p e r a tu r e

Women.

T h e f l u c t u a t i o n in th e b a s a l t e m p e r a t u r e of w o m e n

d u r in g th e r e p r o d u c t i v e c y c l e h a s b e e n r e v i e w e d by T o m p k i n s (1944),
and r e c e n t l y by W h ite l a w (1952).
A r e v i e w of the l i t e r a t u r e d e a li n g w ith the d e t e r m i n a t i o n of
b a s a l t e m p e r a t u r e of w o m e n show s a t y p i c a l c u r v e d u r i n g the m e n ­
s t r u a l c y c le .

T h e t e m p e r a t u r e i s r e l a t i v e l y low du rin g the f i r s t

p a r t of th e c y c l e ; i t d r o p s to a m i n i m u m a b o u t the t i m e when o v u ­
lation o c c u r s .

It then r i s e s

s h a r p l y to a r e l a t i v e l y high le v e l , w h i c h

i s m a i n t a i n e d u n t i l th e n e x t m e n s e s , w h en t e m p e r a t u r e d r o p s a b r u p t l y
(Van de V el d e ,

1904; G r e u l e c h and M o r r i s ,

R u b e n s te i n a n d B i n d l e y ,

1937,

sev eral other investigators).

1939, and

1941; M a r t i n ,

1940; T o m p k in s ,

1943;
1944; a nd

8
G r e u l e c h and M o r r i s

(1941) r e p o r t e d t h a t b e f o r e m a t u r i t y ,

a f t e r th e m e n o p a u s e , a n d i n m e n ,
a r e n o t found.

s im ila r t e m p e r a tu r e fluctuations

T h e y a l s o found t h a t if c o n c e p t io n o c c u r s ,

t e m p e r a t u r e w i l l r e m a i n a t the high p o s t - o v u l a t i o n le v e l.
i m p o r t a n t f e a t u r e i s th e r a p i d

the
T he

r i s e in t e m p e r a t u r e a t o v u la ti o n .

R u b e n s t e i n a n d L i n d l e y (1937) c o r r e l a t e d a stu d y of v a g i n a l s m e a r s
w i th a s t u d y of t e m p e r a t u r e

and found t h a t d u r i n g the p h a s e of f o l ­

l i c u l a r d e v e l o p m e n t the b a s a l r e c t a l t e m p e r a t u r e te n d s to d r o p
progressively.

T h e low p o in t in the t e m p e r a t u r e

w he n th e f o l l i c l e m a t u r e s .
d u c ti o n of p r o g e s t e r o n e ,

ovulation.

reached

A f t e r o v u la tio n and the b e g in n in g of p r o ­

w hich c o u n t e r a c t s in p a r t the t e m p e r a t u r e -

d e p r e s s i n g a c t i o n of e s t r o n e ,
hours before

curve is

the t e m p e r a t u r e b e g i n s to r i s e a few

The t e m p e r a t u r e

l a t i o n a n d s h o u l d e x c e e d 0.5"

rise

continues a f te r ovu­

F a h r e n h e i t in the f i r s t t w e n t y - f o u r

h o u r s a f t e r o v u l a t i o n , a n d 1" F a h r e n h e i t the f i r s t w ee k a f t e r o v u ­
lation.

A s s o o n a s t h e c o r p u s l u t e u m h a s r e g r e s s e d , a few d a y s

b e f o r e m e n s t r u a t i o n , n ew f o l l i c l e s b e g in to de v e lo p .
g i n s to b e p r o d u c e d a g a i n .

E strone b e ­

Since t h e r e i s now no fu n c tio n a l c o r ­

pu s l u t e u m , t h e t e m p e r a t u r e - d e p r e s s i n g

a c t i o n of e s t r o n e i s a g a i n

a p p a r e n t , a n d t e m p e r a t u r e b e g in s to go down.
the c o r p u s l u t e u m p e r s i s t s and t e m p e r a t u r e

D uring p r e g n a n c y

r is e is m aintained.

9
They ad d ed t h a t p r e g n a n c y i s i n d i c a t e d by a p e r s i s t e n t l y high
tem perature

curve.

R o t h c h i l d a n d R a p p o r t (1952) r e p o r t e d t h a t fo llow ing a d o s e
of 10 m i l l i g r a m s of p r o g e s t e r o n e
da ys to c r e t i n s ,

a d m in is te r e d daily f o r eleven

o r 25 to 50 m i l l i g r a m s

of p r o g e s t e r o n e d a i l y f o r

nine d a y s to f e e b l e - m i n d e d m a l e h u m a n s ,
e l e v a t io n in body t e m p e r a t u r e .

th e y a l l

r e s p o n d e d w i th

O t h e r i n v e s t i g a t i o n s by N i e b u r g

and G r e e n b l a t t (1948) s h o w e d t h a t in c a s t r a t e d f e m a l e
a d m i n i s t r a t i o n of p r o g e s t e r o n e i n c r e a s e s
t ha t of the c a s t r a t e d

controls,

rats

the

the t e m p e r a t u r e above

while e s t r o g e n p r o d u c e s a d e c r e a s e

of t e m p e r a t u r e .
W h i tel a w (1952) t e n d e d to b e l i e v e t h a t the u s e of the b a s a l
body t e m p e r a t u r e p a t t e r n a s a r e f l e c t i o n of the o v a r i a n h o r m o n a l
ph ysio lo g y m a y not r e s t on too sound a foundation.
tw e l v e n o r m a l l y m e n s t r u a t i n g

In a stu d y of

w o m e n he found t h a t in s ix of t h e m ,

the t e m p e r a t u r e

f e l l f o r t y - e i g h t h o u r s b e f o r e the flow; in fo u r,

the t e m p e r a t u r e

d r o p p e d t w e n t y - f o u r h o u r s b e f o r e the flow; a nd i n

three,

on the

tem perature

s e c o n d day of m e n s e s ;

while in the r e m a i n d e r the

d r o p p e d a f t e r t his t i m e .

w ho se t e m p e r a t u r e
four ho u rs la te r.

fell b e fo re m e n s e s ,

In t h r e e
it r o s e

of the te n c a s e s
s h a r p l y a g a in t w e n t y -

He a l s o found th a t the a d m i n i s t r a t i o n of 125

10
m i l l i g r a m s p r o g e s t e r o n e p lu s

0.2 m i l l i g r a m s

s t a r t i n g on t h e t w e n t y - s e c o n d day of the

eth in y l e s t r a d i o l

c y c le and continuing t h r o u g h

the se c o n d d a y of b l e e d i n g did n o t p r e v e n t the o n s e t of m e n s t r u a ­
tion o r the f a l l of t h e b a s a l body t e m p e r a t u r e .

He c o n c lu d e d t h a t

e ndo g en o u s p r o g e s t e r o n e i s n o t the h o r m o n e r e s p o n s i b l e f o r t he
r i s e an d m a i n t e n a n c e of the t h e r m o g e n i c e ff e c ts .
T h o ug h B l u n t a n d Dye (1921) r e p o r t e d th a t t h e r e w a s no c o n ­
s t a n t ch an g e i n p u l s e r a t e d u r in g m e n s t r u a t i o n and t h a t t h e r e w a s
no d e f i n i te r e l a t i o n b e t w e e n p u l s e r a t e and l e v e l of m e t a b o l i s m ,
King (1914) found t h a t t he h i g h e s t p o in t of both b a s a l t e m p e r a t u r e
a nd h e a r t r a t e a r e

r e a c h e d t h r e e to f o u r d a y s b e f o r e the m e n s e s ,

a n d t h a t the l o w e s t p o i n t i s a t t a i n e d t h r e e days a f t e r the c e s s a t i o n
of m e n s e s .

K l e i t m a n a n d R a m s a r o o p (1948) r e c o m m e n d e d the u s e

of both body t e m p e r a t u r e a nd h e a r t r a t e
e x a c t d e t e r m i n a t i o n of the o c c u r r e n c e
o b t a in e d by body t e m p e r a t u r e alo n e .

c u r v e s to g e t a m o r e

of ov u lation th a n could be
T h e y found t h a t a n i n c r e a s e

of t en to t w e n t y h e a r t b e a t s p e r m i n u t e i s a p p r o x i m a t e l y equ a l
to a r i s e

of 1 * F a h r e n h e i t in the b a s a l t e m p e r a t u r e .

R ats.

In r a t s ,

B r o b e k (1947) r e p o r t e d th a t low t e m p e r a t u r e s

w e r e c o n s i s t e n t l y n o t e d on the a f t e r n o o n j u s t p r e c e d i n g the ni g ht of

11
h y p e r a c t i v i t y a s s o c i a t e d w i th t h e o n s e t of e s t r u s .

He a l s o o c c a ­

s i o n a ll y found i t low a d a y b e f o r e o r a day a f t e r e s t r u s .
l ow er d u r i n g e s t r u s

It w a s

than d u rin g d i e s t r u s .

T h e I n f l u e n c e of A l t e r a t i o n s in T h y r o id
A c t i v i t y on R e p r o d u c ti o n

H y p o th y r o id i s m

M enstrual cy cle.

C l i n i c a l p a t i e n t s with m y x e d e m a due to

p r i m a r y d y s f u n c t i o n of th e t h y r o i d ha d a m e n o r r h e a n ot a t t r i b u t a b l e
to m e n o p a u s e .

In s u c h c a s e s ,

the n o r m a l o v a r i a n c y cle w as r e ­

s u m e d w ith th e a d m i n i s t r a t i o n of th y r o i d m a t e r i a l s .

Lerm an

(1942) co n c l u d e d t h a t th e m o s t lik e ly ex p lan ation i s th a t the o v a r ­
i a n cy c l e in s u c h c a s e s i s n o r m a l , b ut the flux of h o r m o n e s i s a t
a low l e v e l a s a r e s u l t of the low m e t a b o l i s m of the c e l l s .

Thy­

r o i d a d m i n i s t r a t i o n s t i m u l a t e s the o v a r y to i n c r e a s e the p r o d u c t i o n
of e s t r o g e n a n d p r o g e s t e r o n e , an d the n o r m a l c yc le r e t u r n s .
M a r i n e (1935) n o t i c e d t h a t t h e r e w as i n t e r s t i t i a l gonada l
a t r o p h y in a p a t i e n t wi th m y x e d e m a .
h y p o th y r o i d m o n k e y i s a m e n o r r h e i c
two p e r i o d s a y e a r .

Engle (1946) showed t h a t the
to the e x te n t of about one o r

B u t when t r e a t e d with a v e r y low do se of

t h y r o i d f o r t e n d a y s , t h e n o r m a l c y c le a lw a y s r e t u r n e d .

The

12
m o n k e y s t h a t w e r e t r e a t e d with t h i o u r a c i l showed i r r e g u l a r
Am enorrhea or

cycles.

e x t r e m e l y p ro lo n g e d c y c l e s of o v e r fifty d a y s w e r e

the r u l e .
H ert^ler

(1942), i n h i s book ' ' D i s e a s e s of the T h y r o id

G l a n d , ' ' p o i n t e d o u t t h a t when the e n l a r g e m e n t of th y ro id of g o i t r u s
w om en d i s a p p e a r e d f o llo wi n g a p p r o p r i a t e m e d i c a t i o n s , the m e n s t r u a l
trouble a lso d i s a p p e a r e d .
toxic d if f u se g o i t e r i s

E strous
disappearance

cycle.

He a l s o

g r e a t e s t a t the m e n s t r u a l p e r io d .

T h y r o i d e c t o m y in the cow r e s u l t e d in the

of p h y s i o l o g i c a l e s t r u s

tion of t h y r o i d - a c t i v e p r e p a r a t i o n s
havior, a s
e t al.

r e p o r t e d th at eye p r o t r u s i o n in

o r libido.

The a d m i n i s t r a ­

re s to re d n o rm al breeding b e ­

r e p o r t e d b y B r o d y and F r a n k e n b a c h (1942) an d S p i e l m a n

(1945).
Several investigators

s e e m to a g r e e th a t h y p o t h y r o id i s m

c a u s e d e i t h e r b y t h y r o i d e c t o m y o r by the a d m i n i s t r a t i o n of g o i t r o ­
genic s u b s t a n c e s w i l l p r o l o n g the d u r a t i o n of the c y c le , e s p e c i a l l y
the e s t r u s p h a s e .
t a k en f r o m
sistence

R i c h t e r (1933)

thyroidectom ized

oi the

r e p o r t e d th a t v aginal s m e a r s

r a t s with in t a c t o v a r i e s

c o r n i f i e d c e l l s in the v a gin a l s m e a r s .

of t h e s e a n i m a l s

w ere hypertrophied.

showed p e r ­
The u t e r i

13
P a w i c k (1947) r e p o r t e d the o b s e r v a t i o n s m a d e when m i c e
w e r e g i v e n 0.5 to 500 m i l l i g r a m s
ously d a i ly f o r t h r e e
the d o se ,

of m e t h y l t h i o u r a c i l s u b c u t a n e -

to f iv e m o n t h s .

R e g a r d l e s s of the s i z e of

c o m p l e t e a n e s t r u s w a s p r o d u c e d in s ix to e i g h t w e e k s .

The o v a r i e s

s h o w e d m a r k e d c o n g e s t io n , with d e g e n e r a t i o n of the

graafian follicles.

N o r m a l e s t r u s r e a p p e a r e d f if te e n to sixty

da ys a f t e r the d r u g w a s d i s c o n ti n u e d .
K r o h n (1947) s h o w e d th a t the n o r m a l e s t r o u s r h y t h m of
m a t u r e a lb in o m i c e w a s d i s t u r b e d by the da ily s u b c u ta n e o u s i n ­
j e c t i o n of 0.3 m i l l i g r a m s o f p r o p y l - t h i o u r a c i l .

The c y c l e wa s

e i t h e r l e n g th e n e d o r d i s a p p e a r e d .

rhythm returned

T he e s t r o u s

to n o r m a l a f o r t n i g h t a f t e r the c e s s a t i o n of t h i o u r a c i l a d m i n i s t r a ­
tion.
In i m m a t u r e f e m a l e m i c e , S o lim a n and R e in e k e (1952)
found t h a t f e e d i n g t h i o u r a c i l a t th e l e v e l of 0.1 p e r c e n t of the food
c a u s e d c o n ti n u o u s e s t r u s a s judg ed by v a g i n a l s m e a r s .

They n o ­

t i c e d a l s o t h a t o v u l a t i o n d id no t o c c u r i n such t r e a t e d a n i m a l s a s
j ud g ed f r o m a h i s t o l o g i c a l p i c t u r e of o v a r i e s with a l a r g e n u m b e r
of g r a a f i a n f o l l i c l e s a n d th e a b s e n c e of c o r p o r a lute a .

In th y-

r o i d e c t o m i z e d r a b b i t s , h i s t o l o g i c a l e x a m i n a t i o n h a s shown o v a r i e s
t h a t c o n t a in a l a r g e n u m b e r of c l o s e l y p a c k e d f o l l i c l e s of a l a r g e r

14
s i z e th a n the n o r m a l c o n t r o l s .
a f t e r c o it u s ( H o f m e i s t e r ,

O v u latio n d o e s n o t ta k e p l a c e

1894; F r e d r i k s o n ,

1947; and Chu,

1944).

T a t u m (1913) n o t i c e d t h a t the o v a r i e s of t h y r o i d e c t o m i z e d
rabbits

sh owed a d e c r e a s e in the n u m b e r of p r i m a r y f o l l i c l e s , an

increased

s i z e of the f o l l i c l e s , and d e g e n e r a t i v e c h a n g e s i n t he ova.

T h ese data w e r e

c o n f i r m e d by Kunde e t a l . (1929).

T h i s i s i n c o n t r a s t to the r e p o r t of E v a n s an d JLong (1921a)
t h a t t h y r o i d e c t o m y i n r a t s a f f e c te d n e i t h e r the o n s e t of p u b e r t y ,
n o r the l e n g t h of the e s t r o u s c y c le.
K r o h n (1951) found th a t p r e g n a n c y and p a r t u r i t i o n c a n follow
a n o r m a l c o u r s e in the t h y r o i d e c t o m i z e d r a b b it .

H istological e x ­

a m i n a t i o n of th e o v a r i e s of t h y r o i d e c t o m i z e d r a b b i t s

showed few

large follicles,

l a r g e m a s s e s of i n t e r s t i t i a l c e l l s , and a few p r i ­

m a r y oocyte s.

T h e r e w a s no e v id e n c e th a t the n u m b e r of f o l l i c l e s

was in c r e a s e d .

T h i s c o n f i r m s n e i t h e r the o b s e r v a t i o n s of Chu

(1944), who r e p o r t e d the i m p o s s i b i l i t y of ov ula tion a f t e r c o it u s in
thyroidectom ized
e t al.

r a b b i t s , n o r the e a r l i e r

r e p o r t of K o r e n c h e v s k y

(1943), who r e p o r t e d th a t the g e s t a t i o n p e r i o d m a y b e c o m e a s

t w i ce the n o r m a l i n t h y r o i d e c t o m i z e d r a b b i t s .

No s a t i s f a c t o r y e x ­

p l a n a t io n c a n be p r o v i d e d to e x p la in the d i f f e r e n c e s b e tw e e n the

15
t h r e e s e t s of r e s u l t s , th o u g h t h e r e i s a l w a y s th e p o s s i b i l i t y o f
i n c o m p le t e t h y r o i d e c t o m y i n an y of the p r e c e d i n g

R e s p o n s e to g o n a d o t r o p h i n s .

experim ents.

In r a t s , h y p o t h y r o i d i s m w i ll

e n h an ce the e f f e c t i v e n e s s of the f o l l i c l e - s t i m u l a t i n g h o r m o n e a s
s t a t e d by JLane (1935), o r g o n d a t r o p h i n s a s r e p o r t e d by L e o n a r d
(1936), S m e l s e r a n d L e v i n e (1941), a n d J o h n s o n and M e i t e s (1951).
B a r m a n (1940) found t h a t a h y p o th y r o id co n d itio n p r o d u c e d
by t h y r o i d e c t o m y i n c r e a s e d the r e s p o n s e of f e m a l e

r a b b i t s to the

t he u r i n e of p r e g n a n t w o m e n .
The m o u s e

s e e m s to be an e x c e p ti o n .

J o h n s o n and M e i t e s

(1951) showed t h a t h y p o t h y r o i d i s m in d u c e d by t h i o u r a c i l a d m i n i s t r a ­
t i on r e s u l t e d i n a r e d u c t i o n in t h e i r r e s p o n s e to g o n a d o tr o p h i c
h o r m o n e , a s t e s t e d by o v a r i a n w e ig h ts .
L e o n a r d a nd L e o n a r d (1937) s t a t e d tha t while it i s

known

t h a t t h y r o i d e c t o m y e n h a n c e s the e f f e c t i v e n e s s of i n j e c t e d f o l l i c l e s t i m u l a t i n g h o r m o n e , the r e m o v a l of the t h y r o id d o e s n o t e n h a n c e
t he e f f e c t i v e n e s s of the f o l l i c l e - s t i m u l a t i n g h o r m o n e p r o d u c e d by
the a n i m a l s ' own p i t u i t a r y .

T h ey d r e w t h e i r c o n c l u s io n s f r o m

finding th at, in t h y r o i d e c t o m i z e d r a t s , a f t e r six to e ig h t d a y s ,
t h e r e w a s no s i g n i f i c a n t c hange in the n u m b e r of f o l l i c l e s when
c o m p a r e d with the c o n t r o l s .

16

P ituitary g o n a d o tro p h in .
tomized r a ts

(when

P itu ita ry ex tra cts fro m thyroidec­

i n j e c t e d into i m m a t u r e f e m a l e m ice)

c r e a s e d weight of o v a r i e s
extracts from n o r m a l

caused in­

and u t e r i in c o m p a r i s o n to r e s u l t s with

a n im als, as

r e p o r t e d by Stein a n d L i s l e

(1942).
P ituitary e x t r a c t s
duced the g r o w t h o f
ovulation.

th e

f r o m t h y r o i d e c t o m i z e d r a b b it s a l s o i n ­
g r a a f i a n f o l l i c l e s , b u t it did no t c a u s e

Chu ( 1 9 4 4 )

c o n tinued to s a y th a t the hyp o p h y sis of t h y ­

roidectom ized r a b b i t s

i s a p p a r e n tl y d e f i c i e n t in ov ulating h o rm o n e ,

w h e r e a s the f o l l i c l e - s t i m u l a t i n g h o r m o n e m a y be c o n s i d e r a b l y i n ­
creased.

Okans

G estation.
( Ro ss,

and

T a k a n a (1946) c o n f i r m e d C h u 's r e s u l t s .

H ypothyroidism

induced e i t h e r by t h y r o id e c t o m y

1938) o r a d m i n i s t r a t i o n of t h i o u r a c i l ( S e e g a r e t a l .,

and K r o h n ,

1950)

d id

n o t c a u se s t e r i l i t y , b u t it i n t e r f e r e d with

the c o n ti n u a t i o n o f g e s t a t i o n .
f e t al r e s o r p t i o n ,

1946;

T h e r e was a d e c id e d i n c r e a s e of

t h o u g h if d e liv e r e d , the r a t s w e r e n o r m a l and

reproduced n o r m a l l y .
K orenchevsky
of t h y r o i d e c t o m i z e d
p e r io d .

e t al. (1943)

r a b b i t s m ay b e co m e a s long as twice the n o r m a l

K r o h n ( 1 9 5 1)

a norm al co u rse

in

r e p o r t e d that the g e s ta t io n p e r i o d

found that p r e g n a n c y and p a r t u r i t i o n c a n follow

t h e t h y r o id e c to m iz e d ra b b it.

17
H yperthyroidism

D a C o s t a a nd C a r l s o n (1933) showed th a t a d a ily do se of 0.5
to 1 m i l l i g r a m

of d e s i c c a t e d t h y r o id s lig h tly a c c e l e r a t e d and r e l a ­

t i ve l y l a r g e d o s e s of 5 to 10 m i l l i g r a m s d e fin itely r e t a r d e d

s e xu a l

m a t u r i t y i n t h e f e m a l e a l b i no r a t , a s d e t e r m i n e d by the da te of
opening of the v a g i n a .
S o li m a n a nd R e i n e k e (1952) r e p o r t e d th a t m i c e

rendered

s l i g h tl y h y p e r t h y r o i d by f eeding t h y r o p r o t e i n r e a c h e d m a t u r i t y
e a r l i e r th an the n o n t r e a t e d o n e s.
estrous

The a n i m a l s

showed n o r m a l

cycles.
T ho ugh t h y r o i d a d m i n i s t r a t i o n s e e m s to h a s t e n m a t u r a t i o n ,

it a lso d e c r e a s e s

the o v a r i a n we ights of the e x p e r i m e n t a l a n i m a l s .

F l u h m a n n (1934) c a m e to the c o n c lu si o n th a t an o v e r a c t i v e th y ro i d
i n h ib i ts o v a r i a n f u n c t io n .

He found tha t feeding v a r i o u s a m o u n t s

of d e s i c c a t e d t h y r o i d s u b s t a n c e s o r th y ro x in e a d m i n i s t r a t i o n to
im m ature

r a t s d e c r e a s e d the r e s p o n s e of t h e i r u t e r i and o v a r i e s

to g o n a d o tr o p h i c e x t r a c t s .
E r s h o f f (1945) r e p o r t e d that f e m a l e r a t s
on d ie ts co n t a i n i n g

r a i s e d to m a t u r i t y

0.5 to 1.0 p e r c e n t d e s i c c a t e d t h y r o id showed

a m a r k e d in h i b i t i o n of o v a r i a n de ve lop m e n t.

The o v a r i e s r e m a i n e d

inf an t il e both i n w e i g h t and h i s t o lo g ic a l a p p e a r a n c e .

T h e r e w as

18
a l s o a d e c r e a s e in o v a r y w e i g h ts of m i c e fed t h y r o p r o t e i n in
t h e i r d iet.

The d e c r e a s e i n w e ig h t w a s p r o p o r t i o n a l to the a d m i n ­

i s t e r e d d o se of t h y r o p r o t e i n (So lim an and R e in e k e ,

1950).

Ste in e t

a l . (1947) sh owe d t h a t the i n j e c t i o n of 1 m i l l i g r a m of t h y r o x i n e
into the o v a r i a n c a p s u l e of t he m o u s e

retard ed m itosis

of i t s

g e rm in a l epith eliu m .
In a d d i t i o n to t h i s , t h e r e

s e e m s to be a g e n e r a l a g r e e m e n t

tha t e x p e r i m e n t a l h y p e r t h y r o i d i s m ind u c e d by the a d m i n i s t r a t i o n of
thyroid-active m a te r ia ls i n c r e a s e s

the

s iz e of the c o r p o r a lu t e a .

It i s th o u g h t t h a t t h r o u g h i t s a c t i o n on the c o r p u s lu te u m the t h y ­
r o i d i n f lu e n c e s the e s t r o u s
1930).

c y c le

(H ay ash i,

1929; and W e ic h e r t ,

W e i c h e r t (1930) and W e i c h e r t and Boyd (1933) r e p o r t e d t h a t

fe e d i n g r a t s with d e s i c c a t e d t h y r o i d p r o l o n g s the d i e s t r u s p e r i o d
f r o m t h i r t e e n to t w e n t y - f o u r d a y s .

There w ere p e rs is te n t func­

t i on a l c o r p o r a l u t e a s u g g e s t i n g i n c r e a s e d output of the lu te n iz i n g
ho r m o n e .
E v a n s a n d Long (1921b) did not n o tic e any d i s t u r b a n c e in
the c y c l e of the r a t a f t e r f e ed ing f r e s h th y ro id .

One should a l w a y s

r e m e m b e r th a t the r e s u l t s will v a r y with the dose used.
In g u i n e a p i g s , C a m e r o n and A m i e s (1926) r e p o r t e d tha t
fee din g of a d r y e x t r a c t of t h y r o i d in d o s e s of l / l 0,000 and

19
1/40 ,000 of body weight p r o d u ce d a p r o n o u n c e d
e s t r u s without a s t r i k i n g i n c r e a s e i n t h e

lengthening of

du ratio n

Mice t r e a t e d the s a m e way showed a l e n g t h e n i n g
e s t r o u s cy cle , a s well a s the e s t r u a l p h a s e

itself.

of the cycle.
of the whole
Solim an and

Reineke (1952) r e p o r t e d th a t slightly h y p e r t h y r o i d m i c e exhibited
a r e g u l a r e s t r o u s cycle.
Kunde e t al. (1929) found th a t t h e r e

was a n a p p a r e n t i n ­

c r e a s e in the n u m b e r of developing g r a a f i a n f o l l i c l e s and p r i m o r ­
d i a l ova in the o v a r i e s of r a b b its c o n v e r t e d into a condition of
s e v e r e h y p e r t h y r o i d i s m by the i n g e s t i o n

of

th y r o id m a t e r i a l .

Such a n i m a l s c a m e into e s t r u s and o v u l a t e d .
Such r e s u l t s show v e r y c l e a r l y t h a t

not only the dose of

h o r m o n e given, but a l s o the s p e c ie s r e s p o n s e
influ ence on the r e s u l t s to be o b tained b y
It i s of i n t e r e s t to m e n tio n h e r e ,

ha s an im p o r ta n t

t r e a t m e n t with thyroid.

also ,

th a t H e lp e r n and

H e n d r y so n (1935) r e p o r t e d that d i n i t r o p h e n o l , though producing a n
i n c r e a s e d m e t a b o l i c r a t e , did not c o m p l e t e l y in h ib it e s t r u s in the
norm al rat.
siderably.

Ho wev e r, the d i e s t u r a l p e r i o d

was p ro longe d c on ­

20

G u d e r n a t s c h (1915) r e p o r t e d th a t t h y r o id s u b s t a n c e s a d m i n ­
i s t e r e d to f e m a l e r a t s h a d a te n d e n c y to p r e v e n t p r e g n a n c y , a nd
if p r e g n a n c y o c c u r r e d , i t u s u a l l y c a u s e d a b o r ti o n .
H o s k i n s (1910) o b s e r v e d th a t a b o r t i o n w a s f r e q u e n t in g u i ne a
pig s fed th y r o i d .

JLintvareva (1929) found that fe e d in g t h y r o i d to

guin ea p ig s r e s u l t e d in s t e r i l i t y due to the i m p o s s i b i l i t y of ovum
i m p la n t a ti o n i n the u t e r i n e wall b e c a u s e of d e g e n e r a t i o n of the
c o r p o r a lu t e a .

He a d d e d t h a t th is s t e r i l i t y w as t e m p o r a r y ; i t d i s ­

a p p e a r e d with c e s s a t i o n of th y r o i d feeding.
Kunde e t a l . (1929) found t h a t h y p e r t h y r o i d r a b b i t s
into e s t r u s , o v u l a t e d , a nd the o v a w e r e im p la n te d ;

came

b u t the young

w e r e n e v e r b o r n e , due to f e t a l r e s o r p t i o n .
G r u m b r e c h t (1939)

r e p o r t e d th a t the t h y r o i d i n c r e a s e s

w e i g h t of the o v a r i e s of i n f a ntile
of g o n a d o t ro p i c s u b s t a n c e s ,

rats

the

r e c e i v i n g a c o n s t a n t d ose

the i n c r e a s e in w e ig h t b e in g p r o p o r ­

t i o n a l to the d o s e of t h y r o i d .

T h is c o m p l e te ly d i s a g r e e s with the

c o n c lu s i o n s of J o h n s o n and M e i t e s (1950) th a t young f e m a l e r a t s
r e n d e r e d s l ig h t l y h y p e r t h y r o i d by the a d m i n i s t r a t i o n of t h y r o p r o ­
t e i n in the d i e t r e s p o n d e d l e s s to a c o n s ta n t d o s e of g o n a d o t r o p i n
than the r a t s
istration.

that w e re

r e n d e r e d hy p o th y ro id by t h i o u r a c i l a d m i n ­

In the m o u s e , S o iim a n and R ein ek e (1952) sh ow ed t ha t

21

t h e r e i s a s i g n i f i c a n t d e c r e a s e in o v a r y w e ights in m i c e

rendered

s l i g h tl y h y p e r t h y r o i d by giving t h y r o p r o t e i n a t the l e v e l s of 0.0125,
0.025,

0.05,

0.1, and 0.2 p e r c e n t in t h e i r diet.

The d e c r e a s e in

w e i g h t w a s p r o p o r t i o n a l to the d o s e of the th y ro id .
R o g e r s (1910), in h i s
m e n t of e x o p h t h a l m i c g o i t e r ,

r e p o r t on the s y m p t o m s an d t r e a t ­
sa id ,

" I hav e n ot found an e x c e p t i o n

in e x o p h t h a l m i c g o i t e r when the f e m a l e p a t i e n t h a s not s u f f e r e d
w ith e i t h e r a m e n o r r h e a ,
ovaries are

dysm enorrhea o r m enorrhagia.

always la r g e and t e n d e r . "

H os k ins (1911)

The
reported

t h a t in th e c a s e of B a s e d o w ' s d i s e a s e , when the t h y r o i d a c t i v i t i e s
a r e a b n o r m a l , the s e x - f u n c ti o n s
cal o b se rv a tio n s have

li k e w is e a r e a ff ec ted .

Many c l i n i ­

shown m e n s t r u a l d i s t u r b a n c e s d u r in g the

c o u r s e of t h i s d i s e a s e , u s u a ll y a m e n o r r h e a o r i r r e g u l a r i t y of the
o n s e t of m e n s t r u a t i o n .
G o l d s m i t h e_t a l.

(1952) found t h a t s e v e n te e n out of e ig h t e e n

p r e s u m a b l y p r e m e n o p a u s a l p a t ie n ts with t h y r o t o x i c o s i s had o l i go m e n
o r r h e a or a m e n o r r h e a .

T h r e e of th e m with a m e n o r r h e a had e v i ­

de n c e of o v u l a t o r y f a i l u r e and h y p o e s t r i n i s m .

Thirteen

showed

e v i d e n c e t ha t in s p i t e of a s c a n ty o r i r r e g u l a r flow, ov ulation w as
o c c u r r i n g and, t h e r e f o r e ,
p itu ita ry -o v aria n axis.

t h e r e was no m a j o r i n t e r f e r e n c e

The r e m a i n i n g

s ix te e n p a tie n ts

with the

resum ed a

22

n o rm a l m e n s tru a l pattern a fter ap prop riate tre a tm e n t for th y ro ­
toxicosis.
S ev e n out of t e n p r e m e n o p a u s a l m y x e d e m a t o u s f e m a l e p a ­
t i e n t s d e m o n s t r a t e d o v u l a t o r y f a i l u r e and an eighth showed a n i n ­
a d e q u a t e c o r p u s l u t e u m e f f e c t on the e n d o m e t r i u m .
ha d n o r m a l o v u l a ti o n a n d m e n s e s .

The o t h e r two

All r e s u m e d a n o r m a l p a t t e r n

a f t e r r e c e i v i n g d e s i c c a t e d thyroid.*
T h e a b n o r m a l i t i e s w e r e c o n s i d e r e d to be a r e s u l t e i t h e r of
i n a d e q u a t e l u t e i n i z i n g h o r m o n e p r o d u c ti o n o r l o w e r e d e f f e c t i v e n e s s
of the h o r m o n e p r o d u c e d .
A stw o o d (1951) r e p o r t e d t h a t by t r e a t m e n t of n in e te e n w om e n
w ith h y p e r t h y r o i d c o n d i t i o n s with a n t i t h y r o i d d r u g s d u r in g o r s h o r t l y
b e f o r e p r e g n a n c y , t h e y c o m p le te d t h e i r p r e g n a n c i e s and t h e r e w e r e
only t h r e e p r e m a t u r e d e l i v e r i e s .

Six te e n m o t h e r s

a f t e r th e a n t i t h y r o i d t h e r a p y was sto p p e d and t h r e e

r e m a i n e d w e ll
required f u r ­

th er treatm ents.

Horm onal Interrelationships

E f f e c t of T h y r o id on R e s p o n s e to E s t r o g e n

T h e t h y r o i d l e v e l s e e m s to be v e r y c r i t i c a l f o r e s t r o g e n to
induce its effects.

R e i s s and P e r e n y (1928), Van H o r n (1933a,

1933b),

23
M e y e r an d W e r t z (1938), L a n g h a m and G u s ta v s o n (1947), and H i l l
(1948) a l l a g r e e t h a t i n c a s t r a t e

r a t s the a m o u n t of e s t r o g e n i c

s u b s t a n c e n e c e s s a r y to i n d uc e e s t r u s w as i n c r e a s e d t h r e e to five
t i m e s when the a n i m a l s w e r e p r e t r e a t e d with th y ro x in e .
L a n g h a m a n d G u s t a v s o n (1947) found a l s o th a t t h y r o p a r a t h y r o i d e c t o m y r e s u l t e d i n a n i n c r e a s e in the e s t r u s r e s p o n s e to 1.3
m i c r o g r a m s of e s t r o n e .

T h e s e r e s u l t s , the a u t h o r s s a id , show

t h a t the le v e l of t h y r o i d f unction s i g n if ic a n tly a f f e c ts th e r e s p o n s e
to e s t r o n e .

F o r n o r m a l a n i m a l s , the r a t unit w as

1.33 m i c r o g r a m s

a s c o m p a r e d to 2.5 f o r the h y p e r t h y r o i d g r o u p and 0.86 f o r the
t h y r o p a r a t h y r o i d e c t o m i z e d gro u p .

T h e i r h y p o th e s is w as th a t the

e x c e s s of t h y r o x i n e m a y , by i n c r e a s i n g m e t a b o l i s m , h a s t e n the
e l i m i n a ti o n of e s t r o g e n i c com pou nd s f r o m the body.
The t h y r o i d gla nd m i g h t a l s o have a d i r e c t e ff e c t on the
ovary.

L e e (1925) r e p o r t e d th a t the t h y r o id e x e r c i s e s a s t i m u ­

l a tin g e f f e c t on the o v a r y .

He d r e w h i s co n c lu sio n f r o m the f a c t

t h a t the r e m o v a l of the t h y r o id r e s u l t e d i n the p r o lo n g a ti o n of the
e s t r u s cy c l e in the r a t .

Io dine d i s t r i b u t i o n .

Iodine w as r e c o v e r e d f r o m the o v a r i e s

of d i f f e r e n t s p e c i e s of a n i m a l s and h u m a n s a s r e p o r t e d by Ruff
(1933) an d C a r t e r (1932).

T h e r e w a s a g r e a t v a r i a t i o n in the

24
a m o u n t s of i o d i n e r e c o v e r e d f r o m the o v a r i e s by the s e v e r a l
w orkers.

C a r t e r (1932) b e lie v e d th a t su c h d i f f e r e n c e s in iodine

c o n t en t m i g h t h av e b e e n due to v a r i a t i o n in the iodine co n ten t of
the o v a r i e s d u r i n g the d i f f e r e n t s t a g e s of the c y c le .

He a l s o r e ­

p o r t e d t h a t the io d i n e c o n t en t of the o v a r i e s of n e w b o r n b a b i e s
w as l e s s t h a n in t h o s e of a d u lts; i t b e g in s to d r o p with the a p ­
p e a r a n c e of m e n o p a u s e .
iod in e o c c u r s .

He t r i e d to d e t e r m i n e the f o r m in w hich

He could not d e t e c t th y ro x in e in any c o n s i d e r a b l e

p r o p o r t i o n , b u t he found a s u b s ta n c e which induced m e t a m o r p h a s i s
to t a d p o le s .
O r r and L e i t c h (1929) found that iodine of the c o w 's o v a r y
w as c o n c e n t r a t e d p r i n c i p a l l y in the c o r p u s

luteum .

S a l t e r (1949) s t a t e d th a t th y ro x in e iodine is fixed in two
g e n e r a l lo c a t i o n s
and ovary.

The f i r s t is it s a c c u m u la ti o n in the p i t u i t a r y

The s e c o n d i s it s a c c u m u la ti o n in the p e r i p h e r a l

t i s s u e s , p r i m a r i l y the s k e le t a l m u s c l e .

Tyndale and L e v in (1937)

c o n cl u d ed t h a t the t h y r o i d h o r m o n e e x e r t s an in h ib ito r y a c tio n on
the g o n ad s d i r e c t l y and not th ro u g h the p itu ita ry .

T h y r o id - pi tu it a r y
its

influence

on the

r e la t io n s h i p.

reproductive

The thyroid gland may e x e r t

sys te m

through the pituitary gland.

25
E v a n s and Si mp s o n (1929) r e p o r t e d th a t the g o n a d - s ti m u l a ti n g
p r o p e r t i e s of the p i t u i t a r i e s of h y p e r t h y r o i d r a t s w e r e i n c r e a s e d ,
w hile t h o se f r o m h y p o t h y r oid r a t s w e r e l e s s effective than the
n o r m a l o ne s.

On the c o n t r a r y , Stein ahd L i s l e (1942) r e p o r t e d

th at pituita ry e x tr a c ts fro m th y ro id e c to m ize d r a t s

s ti m u l a t e d d e ­

v e l o p m en t of h e a v i e r o v a r i e s and u t e r i when in je c te d into i m m a ­
t u r e m i c e than did e x t r a c t s f r o m n o r m a l a n im a ls .
R ein eke e t al. (1941)

r e p o r t e d t h a t the p i t u i t a r i e s take n

f r o m t h y r o i d e c t o m i z e d k i d s had a l o w e r go na do tropic p o te n c y than
t h o s e tak e n f r o m c o n t r o l s of the s a m e weight.
The a d m i n i s t r a t i o n of e s t r o g e n i c m a t e r i a l s to t h y r o i d e c t o ­
m ized ra ts (Janes,

1946; and B a k e r and E v e r e t t ,

w ith th y r o i d i n t a c t ( B r a d b u r y ,
p i t u i t a r y w e i g h t s.

1947)

1947) o r to r a t s

r e s u l t e d in the i n c r e a s e of

So did t h y r o i d e c t o m y alone ( J a n e s ,

1946).

Baker

a nd E v e r e t t (1947) c a m e to the c o n c lu s io n that this s tim u lati n g
a c ti o n on the p i t u i t a r y i s not m e d i a t e d by the th y ro id , and t ha t i t
m a y be e l i c i t e d in the a d ult a s well a s in i m m a t u r e r a t s .
P a y n e (1944) n o t ic ed th a t t h i o u r a c i l t r e a t m e n t i n c r e a s e s the
th y r o i d weight and h e i g h t e n s the e p ith e liu m , which s u g g e s ts a v e r y
m a r k e d i n c r e a s e in the t h y r o i d - s t i m u l a t i n g potency of the p i t u i t a ry .
H o w ev er , the a s s a y of p i t u i t a r i e s f r o m t h i o u r a c i l - t r e a t e d chicks

26

s h o w e d no s i g n i f i c a n t d i f f e r e n c e in t h y r o t r o p h i c p o t e n c y w h e n c o m ­
p a r e d w it h th e n o n t r e a t e d
there

ones.

H oussay

w a s no c h a n g e i n th e t h y r o t r o p h i c

fo l l o w in g t h y r o i d e c t o m y .
These

This

was

e t a l.

(1932) found t h a t

p o t e n c y of the

ra t pituitary

c o n f i r m e d by S m e l s e r

findings m ig h t su g g e st th at th e r e i s an i n c r e a s e d

th e t h y r o t r o p h i c

h o r m o n e w h ic h p r e v e n t s

any a p p re c ia b le

(1934).

o u tp u t of
storage

in t h e g l a n d .
On t h e b a s i s
se v e ra l investigators
the

of c y t o p h y s i o l o g i c
came

s t u d i e s of th e p i t u i t a r y ,

o u t w ith v a r i a b l e

results

regarding

s i t e of f o r m a t i o n of t h e v a r i o u s h o r m o n e s of the p i t u i t a r y .

The h o rm o n e s

that a r e

of i n t e r e s t to u s h e r e a r e

phic an d g o n a d o tr o p h ic h o r m o n e s .

There

seem s

the t h y r o t r o ­
to be u n a n i m i t y

of o p in i o n t h a t t h e o r i g i n of th e f o l l i c l e - s t i m u l a t i n g h o r m o n e i s
in t h e b a s o p h i l s .
Severinghaus
B renem an

This is

(1937) w i t h r a t s ,

cells

thyrotrophic

are

Payne

(1947) with c h i c k s , a l s o

( 1941) , a n d S c h o o l e y a n d R id d l e (1938) in the pig eo n .

S everinghaus
secrete

s u p p o r t e d by t h e c y t o l o g i c a l w o r k of

th e

(1937,

1939) i s of th e i d e a t h a t a c i d o p h i l s

horm one.

He a l s o b e l i e v e s t h a t th e b a s o p h i l i c

s i t e f o r f o r m a t i o n of f o l l i c l e - s t i m u l a t i n g h o r m o n e .

H e n o t i c e d t h a t e s t r o n e a c t i v a t e d the s e c r e t o r y
s o p h i l s to s u c h a n e x t e n t a s

c y c l e of the b a ­

to r e s u l t in f in a l e x h a u s ti o n .

27
M o rris

(19 52 ) s h o w e d t h a t e s t r o n e a d m i n i s t r a t i o n i n h i b i t s

th e d e v e l o p m e n t o f b a s o p h i l s a n d r e s u l t s

in the p r e s e n c e

acidophils.

in t h y r o i d a c t i v i t y a n d

T here

w as a lso an i n c r e a s e

thyrotrophic horm o n e
acidophils as

of

p o t e n c y of the p i t u i t a r y w h ic h p o i n t s

the a c ti v e

to t h e

c e l l ty p e i n p r o d u c i n g t h y r o t r o p h i c h o r m o n e .

T h e e f f e c t of a n d r o g e n t r e a t m e n t on the p i t u i t a r y g a v e a
picture

sim ilar

to t h a t of e s t r o n e ,

T he p i t u i t a r i e s
thyrotrophic

of t h i s g r o u p did n o t show a d i f f e r e n c e in t h e i r

potency over

Zeckw er
thyroidectom y

th o u g h i t w a s n o t a s g r e a t .

et al.

there

su g g ested that th e se

t h a t of the u n t r e a t e d b i r d s .

(1935) found, on the o t h e r ha nd ,

w a s a v a c u o l a t i o n of the b a s o p h i l i c
thyroidectom y cells

secrete

th a t a f t e r
c e i l s he

the t h y r o t r o p h i c

horm one.
Payne

(1944) i l l u s t r a t e d a l s o

the a p p e a r a n c e of t h y r o i d e c t o m y

c e l l s i n c h i c k p i t u i t a r i e s a n d he a g r e e d with p r e v i o u s i n v e s t i g a t o r s
th a t t h e t h y r o i d - s t i m u l a t i n g
He

s till thought,

principle is

h o w e v e r , t h a t th e y a r e

s e c r e t e d by the b a s o p h i l s .
not s y n o n y m o u s with t he

b a s o p h i l s of c a s t r a t i o n .
O ther in v e s tig a to rs as
H alm i

(1950) b e l i e v e

a nd d e l t a c e l l s .

R om eris

that th e re a r e

(1940), G o m o r i

(1950), a nd

two t y p e s of b a s o p h i l s :

beta

H a l m i (1950) c o n c l u d e d th a t the d e l t a c e l l s a r e

the

28
m o st likely so u rc e

of b o t h f o l l i c l e - s t i m u l a t i n g a n d t h y r o t r o p h i c

horm one.
Purves
observe

and G r ie s b a c h

two t y p e s of c e l l s

a n t e r i o r p i t u i t a r y of t h e

(1951a,

erties

and

rat.

r e a c t i o n to c h a n g e s

fluctuations,
horm one.

situated

e d g e of t he p a r s

The

r e s p o n d s o n ly to t h y r o x i n e
in the a m o u n t of g o n a d a l

situated som ew hat m edially
r e s p o n d on ly to

nam ely estra d io l benzoate,

in the a m o u n t of t h y r o x i n e .

t r u e o n ly f o r m o d e r a t e

T hi s

doses o r

to t h e p h y s i o l o g i c a l l e v e l .

The a u th o rs
benzoate o r

size,

and t h e ir staining p r o p ­

interm edia

in t h e g o n a d a l h o r m o n e s ,

unaffected by v a r ia tio n s

close

in the

in the h o r m o n a l e n v i r o n m e n t .

centrally

s p e c i f i c i t y of r e s p o n s e h o l d s
doses

size

O n t h e o t h e r h a n d , th e c e l l s

fluctuations
a nd a r e

regional distribution,

a n d i s u n a f f e c t e d by c h a n g e s

b e n e a t h th e l a t e r a l

a b le to

T h e s e t y p e s of c e l l s d i f f e r in t h e i r

in t h e i r g r a n u l e

g r o u p of c e l l s t h a t i s

1951c) w e r e

containing gly co p ro tein g ra n u le s

s h a p e , a f f i n i t y to t h e b l o o d v e s s e l s ,
and m o s t i m p o r t a n t ,

3951b,

a lso o b s e r v e d that la r g e

thyroxine

depress

d o s e s of e i t h e r e s t r a d i o l

b o th ty p e s of c e l l s .

p r o l o n g e d a d m i n i s t r a t i o n of t h y r o x i n e

E xcessive o r

r e s u l t e d in a n i n c r e a s e

the a m o u n t of g l y c o p r o t e i n i n the g o n a d o t r o p h i c c e l l s ,
t u r e of a p i t u i t a r y w h i c h is

sim ilar

in

giving a p i c ­

to t h a t p r o d u c e d by go na da l

29
insufficiency,

though l e s s

extensive.

T h i s m i g h t p o s s i b l y be due

to a n i m p a i r m e n t of g o n a d a l f u n c tio n ( S e v e r i n g h a u s ,

1937).

T hyroid O vary R elationships

T h e e f f e c t s of c a s t r a t i o n of f e m a l e a n i m a l s on t h y r o i d
activity.

This is an a r e a

of i n v e s t i g a t i o n w h e r e a n i n v e s t i g a t o r

m i g h t t h i n k b y th e f i r s t look a t the l i t e r a t u r e
a g r e e m e n t b e t w e e n th e s e v e r a l i n v e s t i g a t o r s

that th e re is a d i s ­
on the e f f e c t s of

c a s t r a t i o n on t h y r o i d a n a t o m y a n d m o r p h o l o g y .

Bu t a l i t t l e

r e a s o n i n g a n d u n d e r s t a n d i n g m i g h t h e lp i n b r i n g i n g out a s in g l e
conclusion.
Loeser

(1934,

1935) c l a i m s t h a t e ig h t e e n d a y s a f t e r c a s t r a ­

tion, t h e t h y r o i d g l a n d of f e m a l e g u in e a p ig s i s m o d e r a t e l y
lated.

T h e p r o d u c t i o n of T. S. H. w a s a l s o i n c r e a s e d .

stim u­

He found

t h a t th e p i t u i t a r y g l a n d of a c a s t r a t e d g u in e a pig, when i m p l a n t e d
into a n o r m a l a n im a l,

w i l l c a u s e a n i n c r e a s e d a c t i v i t y of the t h y ­

r o i d g la n d g r e a t e r t h a n t h a t in d u c e d f r o m n o r m a l n o n c a s t r a t e d
an im als.
K i p p en a n d L o e b (1936) r e p o r t e d th a t g o n a d e c t o m y in gu i ne a
p i gs d u r i n g t h e e a r l y

s t a g e s of s e x u a l m a t u r i t y i n c r e a s e d the p r o ­

l i f e r a t i v e a c t i v i t y of t h e t h y r o i d gla n d d u rin g the f i r s t w e e k follow ing

30
the o p e r a t i o n .
produces its

T h e y t h o u g h t t h a t t h i s r e m o v a l of f o l l i c u l a r h o r m o n e
e f f e c t on t h e t h y r o i d t h r o u g h the p i t u i t a r y w h e r e i t

elicits an in c r e a s e d

p r o d u c t i o n of T. S. H. a n d F . S. H.

The

thy roid-stim ulating horm one,

they said, m u s t be c o n s id e re d a s

d istinct fro m

effect re p r e s e n ts ,

specific

F.

S. H.

T his

therefore,

a non­

e f f e c t of g o n a d e c t o m y on the a n t e r i o r p i t u i t a r y .

im m ature

g u in e a p i g s , the a u t h o r s

r e p o r t e d t h a t the

In young

changes w ere

«

less

definite

than in o ld e r

ti o n i n f e m a l e
proliferative

g u in ea pigs

activity,

ones.

Ch o u k e

(1930) found t h a t c a s t r a ­

c a u s e s no a p p r e c i a b l e

n o r i n the

structural

change in the

characteristics

of the

th y ro id gland.
o tarr
gross

and B ru n e r

histologic

(1935) a l s o

c h a n g e s f o und in th e t h y r o i d s of f e m a l e

p i g s e i g h t e e n to t h i r t y - t h r e e
ported that c a s tr a t e d
thirty days a f te r

th e

days a fte r

castration.

response

g u in e a

They a lso

re­

l e m a l e g u i n e a pig s r e s p o n d e d to T. S. H.

c a s t r a t i o n w it h h i s t o l o g i c

not d ifferen t fro m
m etabolic

r e p o r t e d t h a t t h e r e w e r e no

n o rm al noncastrates.

c h a n g e s in t h e t h y r o i d

T h e y a d d e d t h a t the

of c a s t r a t e d g u in e a p i g s to T. S. H. w a s of

sam e m agnitude a s

w a s th e

response

T h e t h i r d g r o u p of i n v e s t i g a t o r s
a longer in te r v a l a f te r

castration.

of the n o n c a s t r a t e s .

studied th y ro id a ctiv ity a t

A n d e r s e n an d K enn edy (1933)

31
re p o rted that th e re
after castratio n .

w as a definite th y ro id atro p h y eight w eeks

B u t t h e y r e p o r t e d t h a t t h e r e w e r e no c h a n g e s

in t h y r o i d h i s t o l o g y o ne w e e k a f t e r th e o p e r a t i o n , a n d s o m e a n i ­
m als

showed a tro p h ie d th y ro id s
£m ge

and L a q u e u r

t h r e e w e e k s a f t e r the o p e r a t i o n .

(1941) r e p o r t e d t h a t w i t h d r a w a l of o v a r i ­

a n h o r m o n e s b y c a s t r a t i o n of r a t s

d e c r e a s e d th e ir thyroid a c tiv i­

t i e s , a s i n d i c a t e d m o r p h o l o g i c a l l y by t h e i r f o l l i c u l a r
in creased
Laqueur

storage
( 1 94 1 a)

of c o l l o i d .

reported

c e l l s a n d t he

In a n o t h e r r e p o r t , S c h ill in g a n d

t h a t in r a t s

with h y p e r p l a s t i c t h y r o i d s ,

c a s t r a t i o n h a d no e f f e c t on t h y r o i d w e ig h ts .
From

such re p o rts ,

one would co n c lu d e th a t th e e f f e c t of

g o n a d e c t o m y on t h y r o i d a c t i v i t y v a r i e s
o p e r a t i o n an d t h e a g e a t the o p e r a t i o n .
two w e e k s a f t e r ' c a s t r a t i o n ,

T h e a c t i v i t y of the t h y r o i d g l a n d s

to d e c l i n e w i t h i n c r e a s i n g t i m e a f t e r the o p e r a t i o n .

So m e a u t h o r s
th a t t h e r e

It s e e m s t h a t a b o u t one to

the t h y r o i d a c t i v i t y i s i n c r e a s e d a s i n ­

d i c a t e d by h i s t o l o g i c a l s t u d i e s .
then s t a r t s

with the i n t e r v a l a f t e r t he

e x a m i n e d i t a t a f a i r l y long p e r i o d and r e p o r t e d

w ere

no c h a n g e s

c o m p a r e d to the c o n t r o l s .

O thers

studied it a f t e r

l o n g e r p e r i o d s a n d r e p o r t e d t h a t the t h y r o i d g l a n d s

w ere atrophic.

It was also

c u r in i m m a t u r e

anim als.

r e p o r t e d th a t s u c h c h a n g e s do n o t o c ­

32
The effects
H ere also,

there

of e s t r o g e n i c

are

c o m p o u n d s on t h y r o i d a c t i v i t y .

som e factors

t h a t i n f l u e n c e the r e s p o n s e

the t h y r o i d g l a n d to e s t r o g e n t r e a t m e n t ,

of

s u c h a s th e d o s e a d m i n ­

i s t e r e d a n d t h e d u r a t i o n of i t s a d m i n i s t r a t i o n .
P in cu s and W e rth essen
v a r i o u s d o s e s of e s t r i n

(1933) i n v e s t i g a t e d th e e f f e c t s of

giv en f o r d i f f e r e n t p e r i o d s .

T h e i r d a t a on

t h y r o i d w e i g h t s i n d i c a t e d a n i n c r e a s e i n w e i g h t a s a r e s u l t of
e s tr in injection.

C u r i o u s l y e n ou gh , the a u t h o r s

data in d ic ate d th at this weight i n c r e a s e
d a y s of i n j e c t i o n , a n d d e c r e a s e s

said th at th e ir

i s a t a m a x i m u m a f t e r five

f a i r l y g r a d u a l l y to a m i n i m u m

a f t e r f o r t y d a y s of i n j e c t i o n a s th o u g h t h e r e i s an i m m e d i a t e e f ­
f e c t of e s t r i n i n j e c t i o n w h i c h c o n ti n u e d i n j e c t i o n d o e s n o t s u s t a i n .
T h e r e w a s no i n d i c a t i o n of a d o s a g e
the p o s s i b l e

r e l a t i o n to th is e f f e c t, w i th

e x c e p t i o n of o n e - u n i t i n j e c t i o n , w hich a p p e a r s

e f f e c t i v e t h a n t h e h i g h e r d o s a g e s of 2, 4, 7, and
F r e u d e n b e r g e r a n d C l a u s e n (1937) a l s o

less

10 r a t - u n i t s .

r e p o r t e d t h a t w ith p r o l o n g e d

a d m i n i s t r a t i o n of t h e e l i n a t a d o s e of 200 i n t e r n a t i o n a l u n i t s e v e r y
o th e r day fo r
decrease
treated

s e v e n t y - f i v e to s e v e n t y - n i n e d a y s ,

they o b s e r v e d a

of 18 p e r c e n t i n the w e i g h t s of the t h y r o i d s of s u c h

rats

w h e n c o m p a r e d to t h e i r

controls.

33
E m g e and L a q u e u r

(1941), a n d S c h i ll in g a n d L a q u e u r

r e p o r t e d t h a t e s t r o n e h a d no e f f e c t on t h y r o i d w e i g h t s
hyperplastic

(1941b)

of t h y r o -

rats.

D ifferent re s u lts

w ere

r e p o r t e d by K r e i t m a i r

and S ieckm ann

(1945), who f o u n d i n h i s t o l o g i c a l e x a m i n a t i o n t h a t the t h y r o i d g l a n d s
of i n f a n t i l e

rats

in j e c t e d with d i e t h y l i s t i l b e s t r o l w e r e in a

resting

c o n d i t i o n an d f i l l e d w i th c o l lo id .
K o e n ig e t a l .
30 m i c r o g r a m s

(1945) r e p o r t e d t h a t w ith the a d m i n i s t r a t i o n of

of e s t r o n e o r

to you ng f e m a l e

rats

9-4 m i c r o g r a m s

d a i l y f o r tw e lv e w e e k s , th e y found t h a t the

i o d i n e c o n t e n t of t h e i r t h y r o i d s w a s
N akam ura

of d i e t h y l s t i l b e s t r o l

less

th a n t h a t of t h e i r c o n t r o l s .

(1932) w a s the f i r s t i n v e s t i g a t o r to st u d y the e f ­

f e c t s of th e h o r m o n e s

of t h e p l a c e n t a ,

pituitary,

i o d i n e c o n t e n t s of t h e t h y r o i d g la n d i n r a b b i t s .
m arkedly accelerated
I

th e r a t e

e x c r e t i o n in the u r in e .

roidectom ized
rates

iodine e x c r e t i o n i s
factors
nancy.

P lacental ex tracts

a n d s l i g h t l y i n c r e a s e d the a m o u n t of

I n j e c t i o n of p l a c e n t a l e x t r a c t s in t h y -

r a b b i t s p r o d u c e d no m a r k e d

o r a m o u n t of I .

and o v a r y on t he

excreted.

ch a n g e in e i t h e r the

The a u th o r 's

conclusion was that

c l o s e l y r e l a t e d to t h y r o i d , w hich i s

resp o n sib le for in creasin g

the m e t a b o l i c

rate

one of the

d u r in g p r e g ­

34
D e sc lin and E r m a n s

( 1 9 5 0 ) r e p o r t e d th a t in r a t s

estradiol

b e n z o a t e w a s found to s ti m. x x la.te t h y r o t r o p i c a c t i v i t y of the p i t u i t a r y .
Few e x p e rim e n ts h a v e
f e c t s of E s t r o g e n s

on t h y r o i d

The e a r l i e s t p a p e r

c a s tra te d fem ale

z o a t e in d o s e s

a c t i v i t y using 1*^* a s an index.

found

who s tu d i e d th e f o u r - h o u r
rats,

b e e n co nd uc ted to i n v e s t i g a t e the e f ­

w as that by P a s c h k i s e t al.

x x p ta k e of I

rats ,

131

by t h y r o i d g la n d s in f e m a l e

a n d castrated

of 50 m i c r o g r a m s

(1948),

r a t s given e s t r a d i o l b e n ­

p e r day f o r twelve d a y s , e l e v e n

d a y s , an d t h i r t e e n d a y s .

X h x e i r d a ta i n d i c a t e d th a t t h e r e w e r e no

d i f f e r e n c e s in t h e u p t a k e

of

sixty-four days a fte r

treated

th a t of the c a s t r a t e d

a lso ,
w ith.

rats

controls

uptake by the th y r o id g l a n d s

c o n tro ls.
(1949) showed th a t the output h a l f -

hexene w as twice the h a l f - t i m e
In a n o t h e r e x p e r i m e n t ,

on the t u r n o v e r

in f e m a l e

when c o m p a r e d to t h e i r

that 1 ^ ^

f r o m th e t h y r o i d

(1952) d e m o n s t r a t e d

131

e s t r a d i o l b e n z o a te did not d if f e r f r o m

E p stein and W o l t e r i n k
t im e of 1 ^ ^

t r a c e r dose of I

ca stratio n

w ith the o v a r i e s i n t a c t ;
of the a n i m a l s

a

the

effect

r a t e of i o d i n e

T he y found t h a t a d o s e

of

gla n d s of c h ic k s given d i a n i s y l of c o n t r o l s .
W olterink et. al.

(1950) and W o l t e r i n k

of v a r i o u s d o s a g e s of d i a n i s y l - h e x e n e
in the th y r o id s of r a t s and m i c e .

1 m icrogram

of e s t r o g e n p e r day f o r

35
three days in c r e a s e d
a nd m i c e .

t h e o u tp u t of I

131

by the t h y r o i d in bo t h r a t s

T h e y a l s o f o u n d t h a t 10 m i c r o g r a m s

g r a m s of e s t r o g e n g i v e n d a i l y f o r t h r e e
s i n g le d o s e d e p r e s s e d I

131

p o r t e d t h a t 50 m i c r o g r a m s
f o r ten d a y s

z o a te d a i l y f o r n i n e d a y s
not i n f l u e n c e

turn o v er.

M on ey e t a l.

of e s t r o n e

i n j e c t e d d a i l y into m a l e

or

effects

ovariectom ized ra ts ,

1951)

re­

rats

of e s t r a d i o l b e n ­

50 m i l l i g r a m s d a il y f o r te n d a y s did

of e s t r o g e n .

131

Lee

u p ta k e .

(1927) r e p o r t e d th a t i n

the m e a n h e a t p r o d u c t i o n w a s a b o u t 10 p e r ­

c e n t b e lo w t h e d e t e r m i n a t i o n s b e f o r e
S h e r w o o d ejt a l .
duce f r o m

(1950,

u p ta k e w ith o u t a

A d o s e of 1 m i l l i g r a m

e i t h e r th y ro id w eight o r I

M etabolic

100 m i c r o ­

days, and a ls o a m a s s iv e

c a u s e d a s i g n i f i c a n t r i s e in 1 ^ *

c h a n g e in t h y r o i d w e i g h t .

and

the r e m o v a l of the o v a r i e s .

(1933) r e p o r t e d

t h a t they w e r e a b le to p r o ­

13 to 42 p e r c e n t d r o p in b a s a l m e t a b o l i s m follow ing

i n j e c t i o n of 10 to 8 00 r a t u n i t s of a m n io t in .
S h erw oo d e t al.
the b a s a l m e t a b o l i s m

(1936) a n d S h e rw o o d (1940) found t h a t w hen
of o v a r i e c t o m i z e d - t h y r o i d e c t o m i z e d r a t s w as

i n c r e a s e d by g i v i n g t h e m a t h y r o i d p r e p a r a t i o n ,
m e d i a t e l y by i n j e c t i n g v a r i a b l e
rat-units

daily fo r th re e

the n followed i m ­

d o s e s of a m n i o t i n f r o m 200 to 300

o r f o u r d a y s , the i n i ti a l b a s a l m e t a b o l i c

36
rate w as

r e a c h e d in l e s s

t h a n h a lf the t i m e n e c e s s a r y f o r the

u s u a l r e t u r n to n o r m a l of t h e r a t s
S t i l b e s t r o l g i v e n a t the d o s e
p a re n tly not as effective as
basal m etabolism
wood,

1941).

fem ale

after

r e n d e r e d h y p e r t h y r e o t i c only.
r a t e of 10 m i l l i g r a m s w a s a p ­

a m n i o t i n in h a s t e n i n g the r e d u c t i o n of

the h y p e r t h y r o i d l e v e l w a s a t t a i n e d ( S h e r ­

Z a i n (1937,

1939)

r e p o r t e d t h a t in h y p e r t h y r e o t i c

r a t s , th e i n t r a m u s c u l a r i n j e c t i o n of

progynon B (Schering)

1,000 r a t - u n i t s

of

d a i l y f o r f o u r t e e n d a y s l o w e r e d the m e t a b ­

o l i s m a n d i m p r o v e d l i v e r g l y c o g e n f o r m a t i o n a s c o m p a r e d to the
rats

re n d e re d hyperthyreotic

only.

He c o n c lu d e d t h a t p r o g y n o n

e x c i t e d a w e a k a n t i t h y r o i d a c ti o n .

T h e e f f e c t s of p r o g e s t e r o n e on the t h y r o i d .
stated before,
therm ogenic

i t is w e l l e s t a b l i s h e d t h a t p r o g e s t e r o n e

effect.

exercises

a

The p h y s i o l o g i c m e c h a n i s m th r o u g h w hi c h

progesterone e x e rcise s

such effect has

N i e b u r g a n d G r e e n b l a t t (1948)
rats

As h a s b e e n

r e c e i v e d l i t t l e a t te n t i o n .

r e p o r t e d t h a t in c a s t r a t e d f e m a l e

th e a d m i n i s t r a t i o n of p r o g e s t e r o n e

increases

the t e m p e r a t u r e

a bove t h a t of t he c a s t r a t e d c o n t r o l s , while e s t r o g e n p r o d u c e s a d e ­
c r e a s e of t e m p e r a t u r e .

S i m i l a r r e s u l t s , thou gh l e s s

d e fin it e l y ,

w e r e o b t a i n e d in t h y r o i d e c t o m i z e d —
o variectom ized anim als.

They

a l s o r e p o r t e d t h a t in a d r e n a l e c t o m i z e d - o v a r i e c t o m i z e d r a t s , e s t r o g e n

37
increases

th e t e m p e r a t u r e

a b o v e t h a t of the c o n t r o l s and p r o ­

gesterone induces a fu rth e r
concluded f r o m

r i s e in the t e m p e r a t u r e .

such data that p ro g e s te ro n e

seem s

T he a u t h o r s

to in f lu e n c e

body t e m p e r a t u r e a n d t h a t the a d r e n a l and t h y r o i d g l a n d s c h a n g e
the e f f e c t s of e s t r o g e n a n d p r o g e s t e r o n e

on body t e m p e r a t u r e

to a

certain degree.
R o t h c h i l d a n d R a p p o r t (1952)
m illig ram s

of p r o g e s t e r o n e

r e p o r t e d th a t a d o s e of

a d m i n i s t e r e d d a i l y f o r e l e v e n d a y s to

c r e t i n s , o r 25 to 50 m i l l i g r a m s of p r o g e s t e r o n e
to f e e b l e - m i n d e d m a l e
ature.

10

humans

c a u s e d an e l e v a t i o n of bo dy t e m p e r ­

The d e t e r m i n a t i o n of p r o t e i n - b o u n d

l a t i o n b e t w e e n i t a nd t h e r i s e

d a ily f o r nine da ys

iodine sh o w ed no c o r r e ­

in t e m p e r a t u r e .

T h e y c a m e to the

c o n c l u s i o n t h a t t h e r e i s a l a c k of t h y r o i d m e d i a t i o n o r i n t e r v e n t i o n
in the p h y s i o l o g i c
therm ogenic

p r o c e s s e s by w hich p r o g e s t e r o n e

exerts

it s

effect.

H i s t o l o g i c a l s t u d i e s of the h y p e r p l a s t i c t h y r o i d s of r a t s
t r e a t e d w i th p r o g e s t e r o n e

showed t h a t p r o g e s t e r o n e alone o r p r o ­

g e s t e r o n e p l u s e s t r o g e n a d m i n i s t e r e d p a r e n t e r a l l y w e r e a b le to i n ­
hi b i t h y p e r p l a s i a .
Laqueur

E m g e a nd L*acjueur (1941) and Sc hilling and

(1941) a l s o r e p o r t e d th a t a lth o u g h e s t r o g e n fa iled to c ha nge

38
the t h y r o i d w e i g h t s

of t h y r o h y p e r p l a s t i c

e s t r o n e an d p r o g e s t e r o n e

decreased

T h e o n ly i n v e s t i g a t i o n s

ra ts progesterone

or

the t h y r o i d w eigh t.

w here I

131

w a s u s e d to stud y t he

e f f e c t of p r o g e s t e r o n e on t h y r o i d a c t i v i t y w e r e t h o s e of M on e y ejt
a l . (1950,
gram s

1951).

T heir

r e s u l t s w e r e t h a t a t o t a l d o s e of 50 m i l l i ­

p r o g e s t e r o n e i n j e c t e d in to m a l e

rats

d u r in g a p e r i o d of t e n

d a y s r a i s e d t h e p e r c e n t of r a d i o a c t i v e i o d in e c o l l e c t i o n by the
th yroid.

In t h i s

experim ent progesterone

did not i n f l u e n c e t h y r o i d

w eights.

O v a ry -A d re n a l R elationship

S ti l l in g (1898) found t h a t the a d r e n a l s
during ovulation.

S im ilar

results

of f r o g s h y p e r t r o p h y

w e r e n o t i c e d in p ig e o n s by

Ri dd l e (1923).
F o ster

(1934) f ound t h a t in the g r o u n d s q u i r r e l the a d r e n a l s

hypertrophy during e s tr u s

a nd p r e g n a n c y , b u t u n d e r g o in v o lu t i o n

after parturition.
A n d e r s e n a n d K e n n e dy (1932) r e p o r t e d t h a t t h e r e i s a n i n ­
crease

i n the w e i g h t of t h e a d r e n a l of the r a t a t e s t r u s .

a nd K en n e d y (1933) c o m p l e t e d t h e i r
s t a g e s of th e e s t r o u s

cycle.

A ndersen

study on the a d r e n a l a t the

T h e i r h i s t o l o g i c a l s t u d i e s show e d

39
hypertrophied a n d
diestrus.

They

the a d r e n a l s

m ore

a lso

the a d r e n a l s

th a n du ri ng

r e p o r t e d th a t the h i s t o l o g i c a l a p p e a r a n c e of

of s p a y e d

l a r to th a t of r a t s

a c t i v e a d r e n a l s d u r in g e s t r u s

r a t s , a w eek a f t e r the o p e r a t i o n , was s i m i ­

at estrus.

T hree weeks a fte r

the

operation

atro p h ied .

Z uckerm an

e t aL (1938) found t h a t the a d r e n a l s

f lu c tu a t e in

s i z e in a n a p p r o x i m a t e l y f i v e - d a y r h y t h m in s p a y e d r a t s i n j e c t e d
d a i l y w ith a t h r e s h o l d
a l s o found t h a t t h e
to a n i n c r e a s e d

In n o r m a l a n i m a l s ,

they

gla nd w as l a r g e r a t e s t r u s th a n a t d i e s t r u s , due

size

Hunt ( 1 9 4 0 )

d o s e of e s t r o n e .

of the c e l l s of the zona f a s c i c u l a t a .

found t h a t in the r a t m i t o s i s in the a d r e n a l s

w a s e ig h t to s i x t e e n

t i m e s m o r e f r e q u e n t in the a n i m a l s du ri n g

t he m i d - l e u c o c y t i c

s t a g e ( d i e s t r u s ) th a n in the c o r n i f i e d c e ll s t a g e

(estrus).

found t h a t 80 p e r c e n t of the m i t o s e s

He a l s o

w e r e in

t he zo n a f a s c i c u . l s . t a w h e r e the r h y t h m i c a c t i v i t y w a s m o s t m a r k e d .
H e a l s o f o u n d t h a t t h e z on a g r a n u l o s a e x h i b i ts th e g r e a t e s t n u m b e r
of m i t o s e s

d u rin g

reasonable

c o r r e l a t i o n m a y e x i s t b e tw e e n the a d r e n a l c o r t e x ,

hypophysis, a n d
K oets

th e c o r n if i e d c e l l s ta g e .

Hunt c o n c lu d e d t ha t a

c o r p o r a lu tea.

( 1 9 4 9 ) d e m o n s t r a t e d a v a r i a t i o n in the e x c r e t i o n of

17 - K e t o s t e r o i d s

in

wo men , with id io p a th ic h i r s u t i s m , a m a x i m u m

-

40
e x c r e t i o n b e i n g o b t a i n e d a t the t i m e of o v u la tio n .
(1949)

D a v is a nd H u l i t

r e p o r t e d a d i s t i n c t e o s i n o p e n i a in w o m e n a t o v u la t io n t i m e

of the c y c l e .
Zondek and B u r s te in

(1952)

re p o rte d that there

is a c y c l i c

v a r i a t i o n in c o r t i c o i d e x c r e t i o n in th e u r i n e of f e m a l e g u in e a p i g s .
The m a x i m a l e x c r e t i o n

ra te was during e s t r u s .

s u l t e d in a lo w a n d a c y c l i c

ou tp u t of c o r t i c o i d s .

O variectom y

The p a t t e r n of

c o r t i c o i d e x c r e t i o n in the m a l e g u i n e a p ig w a s the s a m e
of the o v a r i e c t o m i z e d f e m a l e g u i n e a p i g s .
the a d m i n i s t r a t i o n of e s t r o g e n c a u s e s

d isch arg e ACTH.
any c y c l i c

as

that

Th ey a l s o found t h a t

an a l m o s t i m m e d i a t e i n c r e a s e

of u r i n a r y c o r t i c o i d s i n b o t h i n t a c t a n d s p a y e d f e m a l e
They a s s u m e d t h a t e s t r o g e n s

re­

anim als.

s t i m u l a t e the a n t e r i o r p i t u i t a r y to

V e n n i n g and K a z m i n (1946)

v a r i a t i o n in t h e e x c r e t i o n of

w e r e not able to fi nd

17 - k e t o s t e r o i d s

in n o r m a l

w om en .
It h a s b e e n e s t a b l i s h e d by s e v e r a l
d o s e s of e s t r o g e n e n l a r g e
of the c o r t e x ,
T his

as

the a d r e n a l s

investigators

th a t l a r g e

m a i n l y due to h y p e r t r o p h y

r e p o r t e d by H e s k e t t and H offm an (1943).

a r e a of e n d o c r i n o l o g y h a s b e e n r e v i e w e d b y T e p p e r m a n ,

E n g e l , an d L o n g (1943); H a r t m a n and B r o w n e ll (1949);
a n i B u r s t e i n (1952).

and Zonde k

41
H a r t m a n a n d B r o w n e l l (1949), i n t h e i r book " T h e A d r e n a l
G land,"

re v ie w e d the l i t e r a t u r e

g e n s on th e a d r e n a l s i n s e v e r a l
m ouse,

h a m s t e r , a n d g u i n e a pig.

c o n c lu d e d t h a t i n a l l t h e s e

d e a l i n g w ith the e f f e c t s of e s t r o ­
s p e c i e s , in c lu d in g the fowl,
From

rat,

t h i s r e v i e w , i t c a n be

s p e c i e s , w ith th e e x c e p t i o n of the m o u s e ,

the a d m i n i s t r a t i o n of e s t r o g e n i c

compounds

r e s u l t s in h y p e r t r o p h y

of t h e a d r e n a l s a n d a n i n c r e a s e i n t h e i r w e ig h t.

T h i s o c c u r s in

sp ayed a s w ell a s in n o r m a l a n i m a l s .
E s t r o g e n s p r o b a b l y a c t t h r o u g h the p i t u i t a r y b e c a u s e e s t r o ­
genic

s u b s t a n c e s f a i l to a c t on the a d r e n a l s a f t e r h y p o p h y s e c t o m y

(B ourne and Z u c k e rm a n ,
In th e m o u s e ,
change

1940).

M artin

(1930) found t h a t e s t r o g e n f a i l e d to

the p i c t u r e of t h e i r x - z o n e w h en a d m i n i s t e r e d o v e r a s h o r t

p e r i o d , b u t p r o l o n g e d a d m i n i s t r a t i o n of e s t r o g e n to i m m a t u r e
c a s t r a t e d and n o rm a l m a le s

and spayed and n o rm a l f e m a le s

re­

s u l t e d i n t h e d e g e n e r a t i o n of t h i s z on e .
T h e e f f e c t s o f e s t r o g e n on the a d r e n a l g l a n d s of the h a m s t e r
h a s b e e n r e v i e w e d by W e x l e r (1952).

He found f r o m h i s

t h a t a s i n g l e i n t r a p e r i t o n e a i i n j e c t i o n of 0.06 m i l l i g r a m s
b e s t r o l given to c a s t r a t e d and sp ayed h a m s t e r s

own w o rk
of s t i l -

caused an in c r e a s e

42
i n t h e a s c o r b i c a c i d c o n t e n t of t h e i r a d r e n a l g l a n d s

to t w i c e t h a t

of the n o r m a l v a l u e s .
R e g a r d i n g t h e e f f e c t of p r o g e s t e r o n e
W i n t e r (1942) a n d L e o n a r d

on the a d r e n a l s .

(1944) sh o w e d t h a t i t f a i l e d to c a u s e

a t r o p h y of th e a d r e n a l s .

T h y ro id -A d re n a l R elationship

T h e e f f e c t s of the T h y r o i d g l a n d on the a d r e n a l s .
tio n al a c tiv ity

T h e func

of th e a d r e n a l g la n d i s in f l u e n c e d in s o m e m a n n e r

by v a r y i n g t h y r o i d a c t i v i t y .
W hen h y p o t h y r o i d i s m
goitrogenic

substances

i s i n d u c e d by the a d m i n i s t r a t i o n of

such a s

s u lf a d r u g s o r t h i o u r a c i l , a s

p o r t e d by L-eblond a n d Hoff (1944), B a u m a n n a n d M a r i n e
F r e e d m a n an d G o r d o n (1950),

th ere is a d e c re a s e

w 'e ig hts, w h ic h i s p a r t l y d u e to d e c r e a s e d
Z a r r o w and Z a rro w
excessive

re­

(1945),

in th e a d r e n a l

s e c r e t i o n of A C T H .

(1951) tho u g h t t h a t t h i s m i g h t be due to t he

p r o d u c t i o n of TSH a t the e x p e n s e of A CT H.

The a d r e n a l a s c o r b ic acid content is a lso d e c r e a s e d ,

as

s how n b y F r e e d m a n a n d G o r d o n (195 0).
I t h a s a l s o b e e n s ho wn by W a ll a c h a n d R e in e k e

(1949) t h a t

f ol lo w in g th e a d m i n i s t r a t i o n of t h y r o i d a l s u b s t a n c e s to a n i m a l s ,

the

43
adrenals enlarge.

The a u t h o r s

r e p o r t e d t h a t the a s c o r b i c a c i d

c o n t en t of the a d r e n a l s d e c r e a s e s
of t h y r o x i n e a d m i n i s t r a t i o n .

to a m i n i m u m a f t e r f o u r d a y s

T h i s i s followed by p r o g r e s s i v e i n ­

c r e a s e s , b o t h i n a d r e n a l w e i g h t a n d a s c o r b i c a c id c o n te n t, t h a t
r e a c h a m a x i m u m a f t e r f o u r w e e k s of th y ro x in e a d m i n i s t r a t i o n .
P e k k a r i n e n e t al.

(1 951) i n v e s t i g a t e d the e f f e c t of a th y r o i d

p r e p a r a t i o n t h y r a n i n e on t h e a d r e n a l s .
m i n i s t r a t i o n of 100 m i l l i g r a m s

T h ey found t h a t the a d ­

of th y r a n i n e da ily f o r a p e r i o d of

tw e n t y d a y s i n c r e a s e d the a d r e n a l w e igh ts of r a t s
a b ov e th e c o n t r o l .

61 p e r c e n t

T his t r e a t m e n t a ls o i n c r e a s e d t h e i r a d r e n a lin

c o n te n t by 88 p e r c e n t , the a s c o r b i c
a nd c h o l e s t e r o l by 85 p e r c e n t .

a c id c o n te n t by 330 p e r c e n t ,

With the a d m i n i s t r a t i o n of 20 to

30 m i l l i g r a m s of t h i o u r a c i l f o r a p e r i o d of t w e n t y - s i x d a y s , the
a d r e n a l w eig hts w e r e

23 p e r c e n t l e s s than the c o n t r o l w e ig h t s ,

b u t a d r e n a l i n i n c r e a s e d by 53 p e r c e n t , a s c o r b i c a c i d i n c r e a s e d by
76 p e r c e n t , a n d c h o l e s t e r a l d e c r e a s e d by 46 p e r c e n t .

T he a u t h o r s

c o n c l u d e d t h a t c h a n g e s i n t h e w e i g h t and c h e m i s t r y of the a d r e n a l
g l a n d s s u g g e s t t h a t a f t e r t h e i n j e c t i o n of t h y r a n i n e the m e d u l l a r y
a n d c o r t i c a l a c t i v i t y a r e i n c r e a s e d , w h il s t a f t e r the a d m i n i s t r a t i o n
of m e t h y l - t h i o u r a c i l a n d m e d u l l a r y a c tiv ity i n c r e a s e d b u t the c o r ­
tical activity is d e c re a s e d .

44
T he e f f e c t s

of s t r e s s

(1949) found t h a t s t r e s s
to h e a t (38* C. ), o r

on t h y r o i d a c t i v i t y .

i n d u c e d by f a s t i n g ,

typhoid v a c c in e ,

et

al.

e x p o s u r e to c o ld (5°

C.),

w a s a s s o c i a t e d w ith a s u b n o r m a l

c o n c e n t r a t i o n of i o d i n e i n t h e t h y r o i d .
v a r i o u s t y p e s of s t r e s s

W illiam s

They also

distinctly d e c re a s e d

re p o rte d that these

the p r o t e i n - b o u n d i o d i n e

in th e s e r u m .
Paschkis

e t al.

caused a d e c re a s e

(1950) found t h a t f o r m a l i n i n j e c t i o n in r a t s

i n t h y r o i d f u n c ti o n a s i n d i c a t e d by th e d i m i n i s h e d

r ,131

u p t a k e of I

M ahorner
cocci,

(1930> found t h a t d o g s i n f e c t e d by i n j e c t i n g

or dogs w hich died f r o m

th e ir thyroids.

p n e u m o n i a sho w ed h y p e r p l a s i a of

He a l s o f ound t h a t a f t e r i n j u r i n g one o r

r e n a l s by c r u s h i n g ,

staphyl-

both a d ­

s e v e n o u t of te n d o g s show ed no c h a n g e , one

showed r e t r o g r e s s i o n ,

a n d two sh o w e d

s l i g h t h y p e r p l a s i a of t h e i r

th y ro id s.
Soffer et a l.

(1949) a n d G a b r i l o v e

et a l. (1950) found t h a t

t he i n j e c t i o n of e p i n e p h r i n e into i n t a c t r a t s
a b l e d e c r e a s e in I

131

uptake.

r e s u l t e d in a c o n s i d e r -

T h e y a l s o found t h a t the a d m i n i s ­

t r a t i o n of c o m p o u n d E i n h i b i t e d th e t h y r o i d - s t i m u l a t i n g
epinephrine.

From

e f f e c t of

t h e s e d a t a , th e y c o n c lu d e d t h a t the a d r e n a l

45
c o r t e x e x e r t s a n i n h i b i t o r y e f f e c t on th e t h y r o i d - s t i m u l a t i n g a c t i o n
of e p i n e p h r i n e .
G abrilove,

et al.

(1950) r e p o r t e d a l s o th a t when 1 7 -h y d r o x y -

11- d e h y d r o c o r t i c o s t e r o n e

w a s a d m i n i s t e r e d t o g e t h e r with e p i n e p h r i n e ,

the t h y r o i d r e s p o n d e d l i k e i n a n i n t a c t r a t giv e n e p i n e p h r i n e a l o n e .
B o tk i n a n d J e n s e n
56 p e r c e n t d e p r e s s i o n

(1951) r e p o r t e d t h a t e p i n e p h r i n e c a u s e d

of t o t a l I

131

c o n t e n t s of the t h y r o i d s a s c o m ­

p a r e d to c o n t r o l v a l u e r .
W illiam s

et al.

(1949) r e p o r t e d t h a t a d r e n a l i n d e c r e a s e s

the q u a n ti ty of p r o t e i n - b o u n d iodine in the s e r u m

of a d r e n a l e c t o m i z e d

rats.
B o tk i n a n d J e n s e n

(1952) found t h a t t h e r e w as an e a r l y d e ­

c r e a s e i n th e t h y r o i d g l a n d c o n te n t of r a d i o a c t i v e iodine a f t e r e i t h e r
epinephrine o r th y ro tro p ic horm one ad m in istratio n .

The s e r u m c o n ­

t e n t of 1*^* a f t e r t h y r o t r o p i c h o r m o n e i n j e c t i o n w a s i n c r e a s e d , p a r ­
t i c u l a r l y th e p r o t e i n - b o u n d c o m p o n e n t, due to a c c e l e r a t i o n of the
production and r e l e a s e
treated rats,
creased.

the

serum

o f t h y r o x in e .

In the c a s e of the e p i n e p h r i n e -

c o n te n t of p r o t e i n - b o u n d iodine w as d e ­

T h e a u t h o r s ' i n t e r p r e t a t i o n w a s t h a t the i n c r e a s e d u t i l ­

i z a t i o n of t h y r o x i n e i n t h e a n i m a l s g iv e n e p in e p h r in e r e s u l t s in a
d e c r e a s e i n t he s e r u m

thyroxine.

Such a lo w e ri n g in the le v e l of

46
th yroxine in the blo od c a u s e s a n i n c r e a s e d p i t u i t a r y r e l e a s e
TSH, an d t h e r e f o r e ,

e p i n e p h r i n e w ill p r o d u c e th e

the t h y r o i d g l a n d a s d o e s

The
activity a s

e f f e c t s of

sam e

of

e f f e c t on

TSH.

the a d r e n a l c o r t e x a n d A C T H on t h y r o i d

s t u d i e d by r a d i o a c t i v e i o d i n e .

In the l a s t few y e a r s ,

co rtiso n e and ACTH have been used extensively for physiological
a nd c l i n i c a l i n v e s t i g a t i o n s .

S e v e ra l in v e stig a to rs have been i n ­

t e r e s t e d i n s t u d y i n g t h e e f f e c t of t h e s e

c o m p o u n d s on t h y r o i d

activity.
A l b e r t (1952) r e v i e w e d the l i t e r a t u r e a c c u m u l a t e d in t he
past three
The
of

years

d e a l i n g w i th t h i s

subject.

f i r s t i n v e s t i g a t o r s who d r e w

c o r t i c a l h o r m o n e s a n d A C T H on the

S o f f e r e t a l ., (1949) a n d W i l l i a m s
Soffer e t al.
ercises

et^ a l.

o u r a t t e n t i o n to the e f f e c t s
thyroid,

u s in g I

, w ere

(1949).

(1949) p o in t e d out t h a t the a d r e n a l c o r t e x e x ­

an i n h i b i t o r y

e f f e c t on th e t h y r o t r o p h i c

e f f e c t s of e p i n e ­

phrine, a s m entioned before.
W ' il li a m s e t a l .

(1949) found t h a t a d r e n a l i n o r a d r e n a l c o r ­

t i c a l e x t r a c t d e c r e a s e d t h e c o n c e n t r a t i o n of I
that it a ls o d e c r e a s e d
serum

by the t h y r o i d a nd

t h e q u a n tit y of p r o t e i n - b o u n d io din e in the

of a d r e n a l e c t o m i z e d

rats.

47
G a b r i l o v e e t a l . (1950) fo un d t h a t the a d m i n i s t r a t i o n of 5
m i l l i g r a m s of A C T H d a i l y f o r tw e lv e

days was

s u c c e s s f u l in a n ­

ta go nizin g the e f f e c t of p r o p y l t h i o u r a c i l in i n c r e a s i n g t h y r o i d
we ight.
H ill e t a l .

(1950)

re p o rte d , h o w e v er, that c o rtiso n e failed

to a l t e r iodine a c c u m u l a t i o n of h y p e r a c t i v e
M o ne y e t al.

(1950,

1951)

t h y r o i d g la n d s .

s t u d i e d the e f f e c ts of a l a r g e

n u m b e r of s t e r o i d h o r m o n e s on t h y r o i d a c t i v i t y .
were m ale

r a t s i n j e c t e d d a i l y w ith l a r g e

a p e r i o d of n i n e to t e n d a y s .

The a n i m a l s u s e d

d o s e s of the s t e r o i d s f o r

Som e of t h e s e

results

hav e b e e n

m e n t i o n e d b e f o r e wh ile r e v ie w in g the e f f e c t s of e s t r o g e n and p r o ­
g e s t e r o n e on th e t h y r o i d .

T he y fo un d t h a t c o r t i s o n e and AC TH

d e c r e a s e d the t w e n t y - f o u r h o u r u p ta k e of I

131

by the t h y r o i d g l a n d s .

They a l s o found t h a t d e s o x y c o r t i c o s t e r o n e did not a f f e c t I

131

up­

ta k e.
S o f fe r e t al.

(1951) r e p o r t e d t h a t I

131

uptake w as

reduced

a f t e r the a d m i n i s t r a t i o n of 5 m i l l i g r a m s of AC TH d a ily f o r f o u r
days in b o th a d r e n a l e c t o m i z e d and i n t a c t r a t s , and t h a t t h e r e w e r e
no d i f f e r e n c e s b e t w e e n the A C T H - t r e a t e d a d r e n a l e c t o m i z e d r a t s o r
r a t s with the a d r e n a l s i n t a c t.

J a c o b s o n e t al.

(1951)

r e p o r t e d that

out of s i x p a t i e n t s with a c t iv e a d v a n c e d H o d g k i n s 's d i s e a s e ,

treated

48
with c o r t i s o n e ,

f iv e s h o we d a r e d u c e d t h y r o i d a c t i v i t y .

The t h y ­

roi d h y p o a c t i v i t y d i s a p p e a r e d w ith in a w e e k following c o r t i s o n e
wi t h d r a w a l .
P a s c h k i s e t al.

(1950) found on the o t h e r hand t h a t both

d e c o x y c o r t i c o s t e r o n e a n d a d r e n a l c o r t i c a l e x t r a c t (Upjohn) f a i l e d
to i n f l u e n c e
roid.

s i g n i f i c a n t l y t he f o u r - h o u r u p ta k e of 1

I t sh ou l d b e m e n t i o n e d , a l s o ,

131

t h a t Money ej; a l.

by the t h y ­
(1950,

1951)

r e p o r t e d th a t b o th s u b s t a n c e s , n a m e l y d e s o x y c o r t i c o s t e r o n e a nd
a d r e n a l c o r t i c a l e x t r a c t (Upjohn), f a i l e d to i n f lu e n c e the tw en t yf o u r h o u r u pt a k e of r a d i o a c t i v e i o d i n e by the th y r o i d .
B o t k in a n d J e n s e n (1951) r e p o r t e d th a t a d r e n a l c o r t e x e x ­
tract,

cortisone,

a n d ACT H a l l f a i l e d to give any s i g n i f i c a n t a l t e r -

, ,131
a t i o n of th e t w o - h o u r u p t a k e of I
C o r t i c a l h o r m o n e s a l s o h a v e b e e n r e p o r t e d to d e c r e a s e
*

the p r o t e i n - b o u n d I
H ardy et al.

13 1

.

,

xn the s e r u m .

(1950) found t h a t the a d m i n i s t r a t i o n of e i t h e r

A C T H o r c o r t i s o n e to p a t i e n t s w ith v a r i o u s
s u i t e d i n a d e c r e a s e i n the

serum

c o ll a g e n d i s e a s e s r e -

protein-bound I

131

of a l l p a ­

tients .
F re d e ric k s o n et ah

(1952) a l s o found th a t m a s s i v e d o s e s
131

of c o r t i s o n e a c e t a t e , b e s i d e s d e c r e a s i n g

c o n s i s t e n t l y the

49
u p t a k e of the t h y r o i d g l a n d s , a l s o
the l e v e l of s e r u m
H ill et al.

r e s u l t e d in a sig n ific a n t fall in

p r o t e i n - b o u n d iodine.
(1950) a l s o found t h a t A C T H a n d c o r t i s o n e i n

n o r m a l s u b j e c t s i n d u c e d a d e p r e s s i o n of I
protein-bound I

131

u p ta k e and s e r u m

131

I t h a s a l s o b e e n r e p o r t e d by W i l l i a m s e t a l.

(1949) t h a t

a d r e n a l c o r t i c a l e x t r a c t s d e c r e a s e d the q u a n ti ty of p r o t e i n - b o u n d
i o d i n e i n th e

serum

of a d r e n a l e c t o m i z e d

rats.

W’i t h a d i f f e r e n t l y p l a n n e d e x p e r i m e n t , A l b e r t e t a l.
r e p o r te d that n e ith e r
c a n t e f f e c t on t h e
the t r a c e r

d o s e of

(1952)

c o r t i s o n e n o r ACTH p r o d u c e d any s i g n i f i ­

secretion rate

of the t h y r o i d .

The u p ta k e of

a fte r tw enty-four hours was, however, d e ­

p r e s s e d by b o t h s u b s t a n c e s .

T he y i n j e c t e d ACTH o r c o r t i s o n e in

r a t s a f t e r t h e i r t h y r o i d s h a d b e e n l a b e le d with 1
a v o i d t h e d i m i n i s h e d i n i t i a l u p tak e of I
h o rm o n e s a r e injected firs t.

131

in o r d e r

to

th a t o c c u r s if both

If the h o r m o n e i n j e c t i o n p r e c e d e d

t he I 131 a d m i n i s t r a t i o n the t h y r o i d s of the e x p e r i m e n t a l r a t s g i ve n
c o r t i s o n e o r A C T H would h av e l e s s to ta l I 131 tha n the c o n t r o l s to
s t a r t w ith .

Thus,

l e s s I * 3 * would be a v a i l a b l e fo r d i s c h a r g e f r o m

the t h y r o i d , w h i c h i n t u r n could lea d to the e r r o n e o u s

c o n c lu s i o n

50
that ACTH o r c o r t i s o n e

interfere

with th e o u t p u t of iod in e f r o m

the g lan d .
H ill e t a l . (1950)
in a s l i g h t d e c r e a s e
nephrotic

syndrom e.

r e p o r t e d t h a t A C T H and c o r t i s o n e

in the b a s a l m e t a b o l i c
They a ls o

rate

resulted

in p a t i e n t s w i th a

r e p o r t e d t h a t A CT H s e e m s

to i n ­

duc e a s l i g h t t e m p o r a r y c l i n i c a l i m p r o v e m e n t in bo th the s o - c a l l e d
thyrocotropic

a nd t h y r o t o x i c v a r i e t i e s of e x o p h t h a l m o s .

B e r s o n et al.
that it is p o s s ib le

(1952),

in the d i s c u s s i o n of t h e i r p a p e r ,

t h a t the h y p o fu n c tio n of the t h y r o i d is

f o r th e u n d e s i r a b l e e f f e c t s of c o r t i s o n e t h e r a p y
bolic v a r i a t i o n s .

said

responsible

r e s u l t i n g in m e t a ­

T h e y a l s o s u g g e s t e d th a t suc h m e t a b o l i c c h a n g e s

c a n b e p r e v e n t e d by the a d m i n i s t r a t i o n of t h y r o i d s u b s t a n c e s o r
t h y r o x in e .
Kuhl a n d Ziff (1952) found th a t in te n p a t i e n t s
o r cortisone,
bolic

rate, o r

r e c e i v i n g A C TH

no s i g n i f i c a n t c h a n g e s w e r e n o te d in the b a s a l m e t a ­
serum

c h o l e s t e r o l l e v e l s a f t e r ten to s i x t e e n d a y s

of A C T H a d m i n i s t r a t i o n .
F rederickson

(1951)

o c c u r r e n c e of t h y r o t o x i c o s i s
A lb e r t e t al.

r e p o r t e d t h a t in A d d i s o n 's d i s e a s e the
is e x t r e m e l y high.

(1952) c o n c lu d e d f r o m t h e i r r e s u l t s

th a t ha ve

been cited e a r l i e r that c o rtis o n e o r ACTH m ight d e c r e a s e

t

I

1 3 1

51
upt a k e due to the i n h i b i t i o n of t h y r o t r o p h i n ,
renal clearan ce

of i o d i d e ,

o r f r o m a d i r e c t i n h i b i t o r y a c t i o n on

the p e r m e a b i l i t y of th e t h y r o i d c e l l s ,
i s m s n e c e s s a r y f o r the
thyroid c e lls, fro m
tors.

o r due to an i n c r e a s e d

o r on any of the m e c h a n ­

s e l e c t i v e a c c u m u l a t i o n of io d id e by the

a n i n c r e a s e d io d id e

T h e y r e p o r t e d t h a t the d i s c h a r g e

space,
of I

131

w a s n o t a f f e c t e d by e i t h e r A CT H o r c o r t i s o n e .
plain such

results

th y ro tro p h in .

T heir

131

1951) o r i t s in h ib iti o n by t h i o u r a c i l a d ­

a re m arkedly

W o o d b u r y ej. a l .
t a k e of I

1951), both the u p ta k e an d d i s ­

lo w e r e d .

(1951) r e p o r t e d a d e c r e a s e in t h y r o i d up-

in h y p o p h y se cto m ized r a t s

TSH, w h en c o m p a r e d w i t h s i m i l a r
TSH a lo n e .

rats

g iv e n both c o r t i s o n e a nd
g ive n the s a m e d o s e of

T h i s m i g h t i n d i c a te t h a t c o r t i s o n e

of TSH on t he t h y r o i d .
tisone

T he y t r i e d to e x ­

r e a s o n i n g w a s th a t in th e a b s e n c e of thyo-

(A lb ert and Tenney,

c h a r g e of 1 ^ ^

f r o m the t h y r o i d

by r u l i n g out the p o s s i b i l i t y of in h ib iti o n of

t r o p h i n ( R a n d a l l e_t a l .,
m inistratio n

o r fro m o th e r fac-

Th e y a l s o

in h ib its the e f f e c t

r e p o r t e d t h a t A C TH a n d c o r „

g i v e n a l o n e did n o t a f f e c t the t h y r o i d a l c o l l e c t i o n of I

131

in h y p o p h y s e c t o m i z e d r a t s , but in h ib it e d the a c ti o n of t h y r o t r o p h i n
gi ve n c o n c u r r e n t l y .

A n o t h e r p o s s i b l e e x p l a n a tio n f o r the d e c r e a s e d uptake of
I

131

in r a t s t r e a t e d with c o r t i s o n e o r ACTH i s the i n c r e a s e d

oi e l im i n a ti o n of I

131

in the u rin e .

B e r s o n et a l. (1952) found

t h a t t h e r e w a s a n e l e v a t i o n of the r e n a l p l a s m a I
rate.

rate

131

clearance

53
E xperim ent I
O xy gen C o n s u m p t i o n . B a s a l T e m p e r a t u r e s , and Body W eig h ts of
F e m a l e R a t s a s C o r r e l a t e d w ith the S ta g e s of the
E s t r o u s C y c le

M a t e r i a l s an d M e th o d s

A clo sed c ir c u it a p p a r a tu s was used for d ete rm in in g oxy­
ge n c o n s u m p t i o n of th e r a t s

( M a c L a g a n and She ahan ,

m o d i f i c a t i o n s i n t r o d u c e d by R e in e k e ) .
t w e lv e d e s i c c a t o r s

The a p p a r a t u s

6 - 1 / 4 i n c h e s in d i a m e t e r .

1950, with
c o n s i s t s of

Each d esiccato r

c o n ta i n e d 200 g r a m s of m o i s t so d a l i m e (Wilson), a t h e r m o m e t e r
w h i c h ca n be r e a d f r o m the o u ts i d e , and a w i r e

s c r e e n on which

the a n i m a l c a n s t a n d w i th o u t touching the sod a l im e o r d i s t u r b i n g
t he t h e r m o m e t e r .
t h r e e - w a y stopcock.

Th e top of e a c h d e s i c c a t o r w as c o n n e c t e d to a
One b r a n c h led to both the d e s i c c a t o r a nd a

m e r c u r y m a n o m e t e r by m e a n s of a T tube, a n o t h e r to a v a c u u m
l i n e , an d the t h i r d b r a n c h to a bag fille d with oxygen.
T h e v o l u m e of e a c h d e s i c c a t o r w as d e t e r m i n e d s e p a r a t e l y
by w eig h in g t h e a m o u n t of d i s t i l l e d w a t e r th a t i t c o n ta in e d when
f i l l e d c o m p l e t e l y , with t h e c o v e r in p la c e .

F r o m the w eight a nd

t e m p e r a t u r e of the w a t e r , t he v o lum e of the d e s i c c a t o r w as c o m ­
pu t e d .

T o t h i s the v o l u m e of the tubing c o n n e c ti o n s to the top of

54
the m e r c u r y on t h e i n n e r a r m
v o l u m e of th e

soda lim e,

of the m a n o m e t e r w a s a d d e d .

screen,

The

and t h e r m o m e t e r w a s s u b t r a c t e d

to giv e th e n e t v o l u m e of the unit.
T h e a n i m a l w a s w e i g he d, p l a c e d in the d e s i c c a t o r a nd the
co v er was

closed.

w a s t u r n e d on.

With th e t h r e e - w a y

The

s t o p c o c k w a s c a u t i o u s l y o p e n e d to the v a c u u m

line to d r a w a n e g a t i v e p r e s s u r e
The

s to p c o c k c l o s e d , the v a c u u m

of 200 m i l l i m e t e r s of m e r c u r y .

s t o p c o c k w a s t h e n t u r n e d to c o n n e c t with the ox ygen line a nd

allow the m a n o m e t e r
t h e n c l o s e d an d the

to c o m e to z e r o p r e s s u r e .

T he

s to p c o c k w a s

s a m e p r o c e d u r e was r e p e a t e d in a l l the tw e lve

units.
T h e wh o le a p p a r a t u s w a s k e p t in an a i r
at a tem perature

c on ditio ne d r o o m

of 24* C e n t i g r a d e ± 1°.

R e a d i n g s w e r e t a k e n f r o m the m a n o m e t e r a t i n t e r v a l s

of

fifteen m in u te s .

T h e r e a d i n g s f r o m the f i r s t t h i r t y m i n u t e s w e r e

usually om itted.

T h i s p e r i o d w as u s u a l l y r e q u i r e d f o r the a p p a r a t u s

to r e a c h t e m p e r a t u r e

e q u i l i b r i u m of 25* C e n t i g r a d e .

I t w a s n e c e s s a r y to tap the m a n o m e t e r b e fo r e
to s e t t l e th e m e r c u r y

c o l u m n.

each readin g

55
C alculations

O x y g e n c o n s u m p t i o n in m i l l i l i t e r s p e r

100 g r a m s body

weight p e r hour:
[V - Va] [ P / 7 6 0 ]
W here

[ 2 7 3 /(2 73 + t)] [1 00 /(b od y weight)]

V = v o l u m e of u n i t in m i l l i l i t e r s
Va = v o l u m e of a n i m a l ( a s s u m i n g t h a t 1 g r a m
P

= pressure

d i f f e r e n c e in m i l l i m e t e r s

= 1 m illiliter)

of m e r c u r y in a n

hour period
t * t e m p e r a t u r e i n s i d e the d e s i c c a t o r
T h e d a i l y o x y g e n c o n s u m p t i o n of t h i r t y - s i x f e m a l e r a t s
determ ined.
units.

Twelve r a t s w e r e

was

r u n s i m u l t a n e o u s l y in i n d iv id u a l

E i g h t d e t e r m i n a t i o n s w e r e ta k e n d u r i n g a p e r i o d of e i g h t

d ay s fo r e a c h r a t in the f i r s t t r i a l .

Fifteen determ inations w ere

t a k e n f o r e a c h r a t in th e s e c o n d g r o u p and ten d e t e r m i n a t i o n s f o r
t he t h i r d g r o u p .

Before

s t a r t i n g the a c t u a l d e t e r m i n a t i o n s t he r a t s

w e r e p u t i n the d e s i c c a t o r on two s e p a r a t e o c c a s i o n s and le ft f o r
a b o u t a n h o u r to g e t u s e d to i t .

B e f o r e e a c h d e t e r m i n a t i o n they

w e r e f a s t e d f o r a p e r i o d of tw e lve to fi f te e n h o u r s .
w e r e taken daily.
rats

V ag ina l s m e a r s

R e c t a l t e m p e r a t u r e s w e r e taken only f r o m

of t h e f i r s t g r o u p .

the

56
R esults

The a v e r a g e

le n g t h of the e s t r o u s

cycles was

5.35 d a y s

( T ab le I).

Body w e i g h t s .

T h e r e w e r e no s ig n i f i c a n t d i f f e r e n c e s b e t w e e n

t he w e i g h t s of th e s a m e a n i m a l s a t the d i f f e r e n t s t a g e s of the
e s t r o u s c y c l e i n a n y of t h e s e e x p e r i m e n t s .

When a l l the d a t a

f r o m t h e t h r e e e x p e r i m e n t s w e r e poo led t o g e t h e r , th e a v e r a g e body
w e i g h t s w e r e 2 1 8 .1 0 g r a m s a t p r o c s t r u s ,

218.85 g r a m s a t e s t r u s ,

219 .2 2 g r a m s a t m e t e s t r u s , an d 219.46 g r a m s a t d i e s t r u s .

Basal te m p e ra tu re .

Though t h e r e w a s a s l ig h t r i s e in the

b a s a l t e m p e r a t u r e d u r i n g e s t r u s , i t was n o t s t a t i s t i c a l l y si g n i f i c a n t .
T he a v e r a g e b a s a l t e m p e r a t u r e s w e r e
estrus,

100.37* F a h r e n h e i t a t e s t r u s ,

100.23* F a h r e n h e i t a t p r o 100.01* F a h r e n h e i t a t

m e t e s t r u s , a n d 100.12* F a h r e n h e i t a t d i e s t r u s .

Oxygen c o n su m p tio n .

Th e oxygen c o n su m p tio n p e r

100 g r a m

bod y w e ig h t p e r h o u r s h o wed a s i g n i f ic a n t r i s e d u rin g e s t r u s a bove
t h a t r e c o r d e d i n a n y of th e o t h e r t h r e e p e r i o d s .
In e x p e r i m e n t 1(a), the a v e r a g e oxygen c o n s u m p tio n in m i l ­
liliters per

100 g r a m s body w eig h t p e r h o u r w as

113.93 a t p r o e s t r u s ,

57
TABLE

I

O z C O N SUMPT ION AND BASAL T E M P E R A T U R E OF F E M A L E
R A T S AT THE VARIOUS STAGES OF THE ESTROUS C Y C L E
Proestrus

Body

weight

B asal

te m p .

02

c o n s u m p t i o n / 100

Body

w e ig h t

0 2 consum ption/100
g m ./h o u r
Body

w ei g ht

0 2 consum ption/100
g m ./h o u r
Body

w ei ght

0 2 c o n s u m p t i o n / 100
g m ./hour

E strus

E x p e r i m e n t 1(a)
205.88
203.75
± 5.23*
± 5.47
100.23
100.37
± 0.93
± 0.18
113.93
139.88
± 4.25
± 5.29’
E x p e r i m e n t 1(b)
220.23
227.05
± 3.54
± 2.84
115 58
101.82
± 1.65
± 2.45'
E x p e r i m e n t 1(c)
212.54
212.35
± 1.25
± 1 12
116 30
101.83
± 2.27
± 1.89'
P o o le d Data
2 18.10
218.85
± 2.42
± 2.04
104.13
120.62
± 2.00’
± 1.49

M et­
estrus

D i­
estrus

208.50
± 7.53
100.01
± 0.22
110.18
± 4.36

203.60
± 4.27
100.12
± 0.10
114.78
± 4.34

225.47
±2.08
99.37
± 1 99

22 4.20
± 2.21
100.66
± 1.32

211.43
±2.69
104.62
± 2.87

215 00
± 1.16
100.68
± 5.29

219 22
± 2.56
102.61
± 1.67

219.46
± 1.48
103.40
± 1.17

* Standard e r r o r .
" SignificantLy h i g h e r (1 p e r c e n t level) than the o t h e r t h r e e
p erio d s.
T he a v e r a g e le n g t h of the e s t r o u s cycle was 5 35 d a y s ±
0.69.
estru s

P e r c e n t i n c r e a s e of O ^ c o n s u m p tio n of the r a t s during
o v e r t h a t d u r i n g d i e s t r u s is equal to 16.65 p e r c e n t .

58
139.88 a t e s t r u s ,

110.18 a t m e t e s t r u s ,

and 114.78 a t d i e s t r u s .

O xy g e n c o n s u m p t i o n i n E x p e r i m e n t 1(b) w a s
115.58 a t e s t r u s ,

99.37 a t m e t e s t r u s ,

101.82 a t p r o e s t r u s ,

and 100.66 a t d i e s t r u s .

E x p e r i m e n t 1(c), the o x y g e n c o n s u m p t i o n w a s
116.30 a t e s t r u s ,

104.62 a t m e t e s t r u s ,

In

101.83 a t p r o e s t r u s ,

and 100.68 a t d i s t r u s .

W h en t h e d a t a a c c u m u l a t e d f r o m the p r e c e d i n g t h r e e e x ­
p e r i m e n t s w e r e pooled to g e th e r,
was

104.13 m i l l i l i t e r s

102.61 a t m e t e s t r u s ,

the a v e r a g e oxygen c o n s u m p t i o n

of o xygen a t p r o e s t r u s ,

120.62 a t e s t r u s ,

a nd 103.40 a t d i e s t r u s .

On th e a v e r a g e , t h e r e w a s a r i s e in oxygen c o n s u m p t i o n of
16.65 p e r c e n t d u r i n g e s t r u s

above th a t d u ri n g d i e s t r u s .

59
E x p e r i m e n t II
1*^* U pta k e by the T h y r o i d G land o f F e m a l e R a t s a t the
S t a g e s of the E s t r o u s Cycle

In the p r e c e d i n g e x p e r i m e n t s i t was found th a t oxygen c o n ­
s u m p ti o n of a d u l t f e m a l e r a t s
t h a n d u r in g the o t h e r t h r e e

is

s ig n if ic a n tl y h i g h e r during

s t a g e s of the e s t r o u s c y c le .

estrus

T h i s l ed

us to do the fo llo win g two e x p e r i m e n t s us ing r a d i o a c t i v e iodi ne
up t a k e a s an i n d e x of t h y r o id a c ti v it y th ro u g h the f o u r s t a g e s of
the e s t r o u s

c y c l e e x p e c t i n g th a t t h e r e m ig h t be a cyclic v a r i a t i o n

in thyroid a c tiv ity in a p a tte rn

that m i g h t c o r r e s p o n d with r e s u l t s

o b t a i n e d f r o m ox yg en c o n s u m p ti o n d e t e r m i n a t i o n s .

M a t e r i a l s and M eth o d s

T h irty -fiv e m a tu r e fem ale
w e r e u s e d in t h i s e x p e r i m e n t .
F a r m s , New City, New Y o r k.

r a t s weighing 250 to 270 g r a m s

Th ey w e r e ob tained f r o m C a r w o r t h
At t h e i r a r r i v a l they w e r e put in

c a g e s and k e p t in a n a i r c on ditione d l a b o r a t o r y a t the t e m p e r a t u r e
of 24° C e n t i g r a d e ±
by D r .

1.

T h ey w e r e fed a n o r m a l r a t i o n f o r m u l a t e d

C. A. H o p p e r t f r o m the C h e m i s t r y D e p a r t m e n t a t Mic hi ga n

S t a t e C o ll eg e .

H i s f o r m u l a f o r 4 k i l o g r a m s is:

60
Y ello w c o r n m e a l

1,400 g r a m s

G r o u n d whole w h e a t

1,000 g r a m s

Whole m i l k p o w d e r (B o rd en )

800 g r a m s

L i n s e e d o il m e a l

400 g r a m s

Alfalfa leaf m e a l

240 g r a m s

B re w e r's

120 g r a m s

T able

y e a s t ( S t r a in G, A. Bu sch )

s a l t (0.01 p e r c e n t Nal)

40 g r a m s

D r in k i n g w a t e r w a s a v a il a b le a l l of the ti m e .
s m e a r s w ere
every

o b t a i n e d f r o m the r a t s d a ily f o r t h r e e d a y s, th e n

si x h o u r s f o r two d a y s.

i n t r a p e r i t o n e a l y with 1 uc. of I
n o rm a l saline

V ag ina l

solution.

E a c h a n i m a l was then i n j e c t e d
131

c o n tain e d in 1 m i l l i l i t e r of a

T he a n i m a l s w e r e i n j e c t e d in g r o u p s of

t h r e e w ith a n i n t e r v a l of five m i n u t e s b e tw e e n e a ch in je c tio n
period.

T he y w e r e

k i l l e d six h o u r s a f t e r the t im e when i n je c t e d

w i th th e r a d i o a c t i v e i o d in e .
T h e a n i m a l s w e r e weighed.
sected,

cleaned carefully,

T h e i r t h y r o id gla n d s w e r e d i s ­

and weighed with a t o r s i o n b a la n c e .

Each

t h y r o i d g l a n d w a s t h e n d i s s o l v e d in 10 m i l l i l i t e r s of a 0.5 N NaOH
s o l u ti o n c o n t a i n i n g 0.5 p e r c e n t N a l to d i s s o l v e a n y l i b e r a t e d iodine.
An a l l e q u o t of 1 m i l l i l i t e r w a s o b ta in e d f r o m
p i p e t t e a n d t r a n s f e r r e d to a p y r e x d i s c .

s u c h so lu tion s by a

T h e s e d i s c s w e r e p u t in

61
an i n c u b a t o r h a v i n g t h e t e m p e r a t u r e

of 90* C e n t i g r a d e f o r two

hours,

s a m p l e s to d r y .

a p e r i o d long e n o u g h f o r th e

The

w ere then t r a n s f e r r e d

to a d e s i c c a t o r c o n t a i n i n g a n h y d r o u s

s u l f a t e an d s o d a l i m e

to a b s o r b

Na CO .
4m

The

sam ples w ere

sam ples
calcium

and p r e v e n t the f o r m a t i o n of

t h e n c o u n t e d by m e a n s

of a G e i g e r

3

counter.

S in c e t h e d r y w e i g h t s

self-absorption co rrec tio n s
renals,

ovaries,

w ere not m ade.

and u t e r i w e r e

surrounding tis s u e s

sim ilar,

T he p i t u i t a r i e s ,

also d is s e c te d cleanly fro m

and w eighed.

m i c r o s c o p i c a l l y by t h e u s e
estrous

of th e t h y r o i d s w e r e v e r y

T he o v a r i e s w e r e

of a l e n s to c o n f i r m t h e

ad­
the

exam ined
s t a g e of t he

c y c l e o b t a i n e d f r o m th e v a g i n a l s m e a r s .
I t w a s n e c e s s a r y to ki ll a l l the a n i m a l s in one day to be

su re that they w e r e
sa m e conditions.
m als

are

a l l t r e a t e d th e s a m e way and k e p t u n d e r

T h is i s the

i n c l u d e d in e a c h

the

r e a s o n t h a t u n e v e n n u m b e r s of a n i ­

s t a g e of th e e s t r o u s

c y c le .

R esults

1*^* uptake .

By Looking a t T a b l e II, one will o b s e r v e

t he

hi g h l y s i g n i f i c a n t i n c r e a s e i n the u p t a k e of r a d i o a c t i v e io d in e by
the t h y r o i d g l a n d s

of t h e e s t r o u s

anim als.

T h e r e w a s a ls o

n i f i c a n t i n c r e a s e i n t h e u p t a k e of the t h y r o i d g l a n d s d u r in g

a sig­

62
TABLE

II

SIX H O U R I 131 U P T A K E BY T H E THYROID G L A N D O F
F E M A L E RATS AT T H E STA G ES O F T H E
EST R O U S C Y C L E
Proestrus

E strus

M etestru s

D iestrus

7

16

6

6

C ounts/sec ./thyroid

1 45.80
± 11.27*

230.51"
± 4.01

1 71 .52 '
± 2 0 .6 4

155.13
± 12.12

C ounts/m g . / s e c .

7.74
± 0.53

11.00"
± 0.63

±

7.79
0.80

7.58
± 0.23

C o u n t / m g . / s e c . / l O O gm.

2.9 0
± 0.30

4.39"
± 0.20

2.93
± 0.32

3.03
0.39

P e r c e n t of d o s e

11.16
± 0.86

17.48"
± 0.73

Num ber

of a n i m a l s

* Standard e r r o r .
' S ig n ifican t at 5 p e r c e n t level.
"

S i g n i f i c a n t a t 1 p e r c e n t le v e l.

12.94
± 1.64

±

11.76
± 0.95

63
m etestru s

ov er th a t during p r o e s tr u s

significantly le s s

or diestrus,

t h a n t h a t t a k e n up d u r i n g

The a v e ra g e

tho ugh i t w a s

estrus.

c o u n t s of t h e t h y r o i d g l a n d s p e r

second w ere

145.80 in t h e p r o e s t r o u s

anim als,

230.51 in the e s t r o u s

171.52 i n t h e m e t e s t r o u s

anim als,

and

anim als,

155.13 in th e d i e s t r o u s

anim als.
W h en t h y r o i d u p t a k e w a s
gram

thyroid p e r

during

of e s t r u s

r a d i o a c t i v e io dine.

the e s t r o u s

take du rin g

estru s

cycle,

The w eights
anim als

rats

had a h i g h e r c a p a c i t y to

T he t h y r o i d w e i g h t s did n o t v a r y

w h ic h i n d i c a t e s

c a p a c i t y to c o n c e n t r a t e

of o r g a n s .

was

T he a v e r a g e

significantly

sm aller

as m entioned b efore,

the a n i m a l s w e r e

d a t a of T a b l e 1 h a v e

already

w e ig h t of th e t h y ­
r a d io a c tiv e iodin e.

body w e i g h t of the

tha n the

re s t because,

picked at ra n d o m .

show n t h a t t h e r e i s

c ha ng e in b o d y w e i g h t w i th s t a g e
T here

t h a t the i n c r e a s e d u p ­

w a s not due to an i n c r e a s e d

r o i d , b u t to a n i n c r e a s e d

estrous

counts p e r m i l l i ­

s e c o n d o r p e r c e n t of i n j e c t e d d o s e , i t w a s a l s o

fo und t h a t th e t h y r o i d s
concentrate

ex p ressed as

of the e s t r o u s

T he

no s i g n i f i c a n t
cycle.

w e r e n o s i g n i f i c a n t d i f f e r e n c e s b e t w e e n th e w e i g h t s

of e i t h e r th e t h y r o i d s

or pituitaries

of the f o u r g r o u p s .

ro id w e ig h ts e x p r e s s e d in m i l l i g r a m s

per

T he t h y ­

100 g r a m s body w e i g h t

64
were

7.11 i n t h e c a s e of p r o e s t r o u s

m als,

8.20 in m e t e s t r u s ,

a n i m a l s , 8.4 3 in e s t r o u s a n i ­

and 8 .1 4 in d i e s t r u s .

T h e a d r e n a l w e i g h t s of th e e s t r o u s
in m i l l i g r a m s

per

100 g r a m s

anim als,

of bo dy w e ig h t, w e r e

h i g h e r t h a n t h o s e of t h e p r o e s t r o u s

anim als.

when e x p r e s s e d
significantly

In t h i s e x p e r i m e n t

a l s o , th e o v a r y w e i g h t s , w h e n e x p r e s s e d in m i l l i g r a m s p e r
gram s

of b o d y w e i g h t ,

m etestrus,

o v e r t h a t of p r o e s t r u s .

w a s a l s o a h i g h ly s i g n i f i c a n t i n c r e a s e in u t e r u s

w eights d u rin g e s t r u s
stages.

showed a significant i n c r e a s e in e s t r u s ,

and d i e s t r u s

T here

100

o v e r t h o s e of the u t e r i of the o t h e r

three

65
TABLE

III

ORGAN W E I G H TS AT T H E S T A G E S O F

T H E ES T R O U S C Y C L E

P roestru s

E stru s

M et­
estrus

D i­
estru s

Body w e i g h t

2 6 7 .5 7
± 11 .14

25 1 .5 6 ''
± 4.21

2 7 0 .4 0
± 13.96

257 .33
± 15.91

T hyroid m g./lO O gm.

7.11
± 1.11

8 .4 3
± 0 .64

8 .2 0
± 0.70

8 .1 4
± 0 .5 4

P itu ita ry m g./lO O gm.

6.35
± 0.48

±

6.81
0.20

5.89
0.47

6.60
± 2.05

A drenal m g ./lO O gm.

17.30
± 1.17

2 1 .8 0 ''
± 1.32

18.79
± 1.73

18.77
± 1.68

O vary m g./lO O gm.

9.45
± 0.45

13.55"
± 0.80

15.13"
± 2.31

15.44"
± 1.46

U teru s m g./lO O gm .

175.86
±11.58

218.55"
± 3.10

180.05
± 7 .14

173.81
± 10.91

"

Significant a t

1 p e r c e n t level.

±

66
E x p e r i m e n t III
1*3^ U p t a k e b y t h e T h y r o i d G l a n d o f F e m a l e R a t s G e t t i n g
S ta n d a r d N a l I n t a k e a t th e S t a g e s o f th e E s t r o u s C y c le

A s d e m o n s t r a t e d in t he p r e c e d i n g

e x p e r i m e n t , we found

t h a t the m a x i m a l u p t a k e of r a d i o a c t i v e i o d i n e w a s a t t a i n e d by r a t s
during

estru s.

In

a t i o n s in t h y r o i d
food i n t a k e

o r d e r to e x c l u d e th e p o s s i b i l i t y t h a t s u c h v a r i ­

a c t i v i t y m i g h t be

during

a nd c o n s e q u e n t l y

the e s tr o u s
in

s i m p l y d u e to th e v a r i a t i o n in

c y c le

as

t h e io d i ne i n t a k e , the

p e a t e d w it h t h e e x c e p t i o n t h a t the iodine
was

F o rty -th ree
average w ere

C arw orth

of 24 ±

m ature

used

e x p e rim en t was

re

in ta k e of a ll the a n i m a l s

1*

and M e th o d s

fem ale

rats

in t h i s e x p e r i m e n t .

F arm s,

c a g e s an d k e p t i n
ture

sam e

standardized.

M aterials

from

r e p o r t e d by B r o b e c k (1947)

w eig h in g
These

New C ity , New Y o r k .

an a ir

180 g r a m s

rats

w ere

They w ere

on t he

obtained
put i n

c o n d it io n e d l a b o r a t o r y ha v ing t e m p e r a ­

C entigrade.

They w e r e
and d r a n k d o u b l e

f e d an I o dine low t e s t d i e t ( R e m in g to n ,
d i s t i l l e d w a t e r f o r f if te e n d a y s .

1937)

The an im als

67
w e r e i n j e c t e d i n t r a p e r i t o n e a l y d a i l y w ith 5 m i c r o g r a m s of N a l c o n ­
ta i n e d in 0.2 m i l l i l i t e r s

of d ou ble d i s t i l l e d w a t e r .

w ere obtained d a ily fo r th re e
experim ent;

th e n the

days

V a g in a l s m e a r s

s t a r t i n g on the te n t h da y of the

s m e a rs w ere

t a k e n e v e r y tw e lv e h o u r s f o r the

l a s t two d a y s , a n d i m m e d i a t e l y a f t e r t h e y h a d b e e n k i ll e d .
l a s t d ay of th e e x p e r i m e n t ,
1 m icrocurie

of I

131

l i t e r of a n o r m a l
groups

they w e r e

i n j e c t e d i n t r a p e r i t o n e a l l y w i th

and 5 m ic r o g r a m s

saline

s o l u tio n .

On the

of Nal c o n t a i n e d in

1 m illi­

T he a n i m a l s w e r e i n j e c t e d i n

of f o u r w i t h a f i v e - m i n u t e i n t e r v a l b e t w e e n e a c h i n j e c t i o n

period.

They w e re

k illed

six h o u r s

a f t e r the t i m e when i n j e c t e d

wi th the r a d i o a c t i v e i o d i n e .
The thyroid

glands w ere d isse c te d ,

w ith a t o r s i o n b a l a n c e ,
discs.

The th y ro id s

perature
third

and p l a c e d a t th e c e n t e r of s m a l l m e t a l

w e r e d r i e d in an oven a d j u s t e d a t the t e m ­

of 9 0 “ C e n t i g r a d e f o r t w e lv e h o u r s , th e n c o u n te d on the

s h e l f of a G e i g e r

d i s s e c t e d o u t,
and u t e r i .

c l e a n e d c a r e f u l l y , w e i g he d

C o u n te r .

T he following o r g a n s w e r e

c l e a n e d and w eighed:

The

ovaries

the v a g i n a l s m e a r

pituitaries,

adrenals,

also

ovaries,

w e r e e x a m i n e d m a c r o s c o p i c a l l y to c o n f i r m

readings.

68
R esults

I

13 1

uptake.

J u s t a s i n th e p r e c e d i n g

was a sig n ific a n t i n c r e a s e

thyroids w ere

also

or d iestro u s

and m e t e s t r o u s

anim als.

22.48 d u r in g p r o e s t r u s ,

during m e t e s t r u s ,

The
values w ere
second,

sam e

tre n d s in I

expressed as

131

counts p e r m i l l i g r a m s

w a s high ,

it w a s

anim als.

u p t a k e w e r e found a l s o when the

of t h y r o i d p e r

of t h y r o i d p e r

100 g r a m s

body

dose.

T he w e ig h ts of o r g a n s .
e n c e s b e tw e e n th e body w e ig h ts ,

T h e r e w e r e no s i g n i f i c a n t d i f f e r ­
thyroid weights, a d re n a l w eights,

o r p i t u i t a r y w e i g h t s of t h e a n i m a l s
The o v a ry w eights

29.63

It will be n o t i c e d

counts p e r m illig r a m

w e i g h t o r p e r c e n t of i n j e c t e d

w ere

44.62 d u r i n g e s t r u s ,

and 24.73 d u r in g d i e s t r u s .

t h a n t h a t of e s t r o u s

anim als over

T h e c o u n t s of th e w h ol e

th a t though the u p ta k e d u r in g m e t e s t r u s

significantly le s s

there

i n th e u p t a k e of r a d i o a c t i v e i o d i n e by

the t h y r o i d g l a n d s of b o t h e s t r o u s
th a t of p r o e s t r o u s

experim ent,

a t the f o u r

of th e a n i m a l s

stages

of th e c y c l e .

k i l l e d when i n d i e s t r u s

s i g n i f i c a n t l y h e a v i e r t h a n t h o s e of a n i m a l s k i l l e d d u r i n g

p roestrus.

The u te ru s

w e i g h t s of the a n i m a l s k il le d d u r i n g e s t r u s

69
TABLE

IV

SIX H O U R I 131 U P T A K E B Y T H E T H Y R O ID G L A N D O F
F E M A L E R A TS AT THE STA G ES O F THE
ESTROUS CYCLE

N u m b e r of a n i m a l s

P ro­
estru s

E stru s

M et­
estru s

D ies­
tru s

13

8

14

8

C o u n ts/sec.

2 2 .48
± 1.60*

4 4 .6 2 ''
± 1.80

29.63"
± 1.69

24.73
± 2 .16

C o u n ts/m g ./sec.

1.55
± 0 .1 4

2.61 •
± 0.18

1.85
± 0.14

1.68
± 0.17

C o u n t s / m g . / s e c . / 1 0 0 gTn.

0.85
± 0.10

1.46
± 0.14

1.03
± 0.10

0.91
± 0.10

P e r c e n t of d o s e

8 .1 7
± 0.64

16.23"
± 0.65

10.79'
dt 0.67

8.99
± 0.78

* S tandard

error.

' S i g n i f i c a n t a t 5 p e r c e n t le v e l .
''

Significant at

1 p e r c e n t le v e l .

70
TABLE

V

ORGAN W E I GH T S AT T H E ST A G E S O F

TH E ESTROUS C Y C L E

P ro­
estrus

E strus

M et­
estrus

D i­
estru s

Body w e i g h t

182.92
=fc 6.60

182.25
± 6.64

180.64
± 2.50

18 4.00
± 2.86

T h y r o i d wt. i n m g . /
100 g m .

8.15
± 0.45

9.48
± 0.33

9.00
± 0.41

8.12
± 0.43

T h y r o i d d r y wt.

2.67
± 0.1 4

2.98
± 0.14

2.79
± 0.41

2.81
± 0.26

P itu ita r y m g./lO O gm.

5.13
± 0.32

±

5.75
0.20

6.11
± 0.36

5.48
± 0.33

A drenal m g./lO O gm.

22.26
± 0.99

24.31
± 2.50

20.87
± 0.87

2 0 .64
± 1.19

O v a r y m g . / 100 g m .

21.08
± 1.20

24.13
± 3.32

2 3.80
± 2.05

26 .4 6 '
* ± 3.18

U te ru s m g./lO O gm.

138.85
± 2.63

230.62"
dfc 19.47

1 5 5 .7 1 "
± 13.49

' Significant a t 5 p e r c e n t level.
11 S i g n i f i c a n t a t 1 p e r c e n t le v e l .

156.38"
± 8.72

✓

71
w ere

sig n ific a n tly h e a v i e r th an t h o s e

the o t h e r t h r e e

stages.

o f t h e a n i m a l s k ill e d d u r i n g

72
E x p e r i m e n t s IV (A) a n d (B)
1*^*

U p t a k e b y t h e T h y r o i d G l a n d of F e m a l e M i c e a t th e
S ta g e s of th e E s t r o u s C y c le

It h a s b e e n pointed out in our re v ie w
one o f t h e
ship a r e

r e a s o n s why i n v e s t i g a t i o n s

co n trad icto ry is

two e x p e r i m e n t s

the

estro u s

sp ecies difference.

cycle

that

of t h y r o i d - o v a r i a n r e l a t i o n ­

w e r e d o n e to c o m p a r e

a ctiv ity d u rin g the

of t h e l i t e r a t u r e

T h e fo llo w i n g

th e p a t t e r n

of t h y r o i d

of m i c e w i t h t h a t o b t a i n e d i n

rats.

M aterials

F ifty m a tu r e
used in th is
F arm s,

experim ent.

The m ic e

w ere

They w e re

2 0 to 25 g r a m s
obtained f r o m
put in cages

and d i s t i l l e d w a t e r c o n ta in in g

5 m illiliters

for th re e

days

w ere

sacrificing

the

w ere

C arw orth
and k e p t
of 24 ±

T h e a n i m a l s w e r e m a i n t a i n e d on low i o d in e t e s t

d ie t (R em ington),
in e v e r y

w e ig h in g

c o n d i t i o n e d l a b o r a t o r y h a v in g t h e t e m p e r a t u r e

1* C e n t i g r a d e .

sm ears

fem ale m ic e

N e w C i t y , Ne w Y o r k .

in an a i r

and M e t h o d s

d aily .

starting

Vaginal s m e a r s

w ere

N al

obtained daily

on t h e t e n t h d a y of t h e e x p e r i m e n t .

then taken e v e r y tw elve h o u r s
anim als.

1 m icro g ram

The

a n d a t th e t i m e of

73

✓

O n th e l a s t d a y of t h e e x p e r i m e n t the m i c e w e r e i n j e c t e d
i n t r a p e r i t o n e a i l y w ith I
solution.

131

c o n t a i n e d i n 0.5 m i l l i l i t e r s

The a n im a ls w e re in je c te d in groups

of f o u r w i t h a f i v e -

m inute in te rv a l betw een each injectio n p e rio d .
six h o u rs

a f t e r b e i n g i n j e c t e d w it h th e

The th y ro id glands w e re

of s a l i n e

They w e re

rad io activ e iodine.

d isse c te d , cleaned carefu lly ,

w e i g h e d w i th a t o r s i o n b a l l a n c e ,

and p l a c e d a t the c e n t e r

m etal discs.

d r i e d in an o v e n a d j u s t e d

tem p erature

The th y ro id s w e re

of 90* C e n t i g r a d e f o r tw e l v e h o u r s ,

w ith a G e i g e r

C ounter at a fixed g e o m e try .

The o v a rie s

to c o n f i r m

reading.

r e p e a t e d u s i n g the

sam e

b e r of a n i m a l s .
w ith

a t the

w ere

the v a g i n a l

of I * 3 * i n s t e a d of 0.5 m i c r o c u r i e

ex­

sm ear

sam e

T h e m i c e i n t h i s E x p e r i m e n t IV (B) w e r e

1 m icro cu rie

preceding

ex p e rim en t was

of s m a l l

th e n c o u n t e d

a m i n e d w i th a b i n o c u l a r m i c r o s c o p e
The

killed

num­

injected

a s i n th e

experim ent.

R esults

I *3 * u p t a k e .

In t h e c a s e

of m i c e , I 131 u p ta k e by th e t h y ­

roid glands had a d iffe ren t p a tte rn
m ice

that w ere

from

t h a t of the

s a c r i f i c e d w h ile in p r o e s t r u s

significant in c r e a s e

in I

131

rats.

The

sh o w e d a s t a t i s t i c a l l y

u p t a k e c o m p a r e d to the

other

s ta g e s in

74
both e x p e r i m e n t s .

In e x p e r i m e n t IV (A) the d i e s t r o u s m i c e

showed a s ig n if ic a n t i n c r e a s e in I
and m e t e s t r o u s

131

u p t a k e o v e r t h a t of e s t r o u s

anim als.

T h e a v e r a g e c o u n t s of t h e t h y r o i d g l a n d s p e r
p e r i m e n t IV (A) w e r e
th e e s t r o u s

anim als,

in the d i e s t r o u s

also

6 7 . 6 9 i n th e p r o e s t r o u s
3 9 . 9 6 i n th e m e t e s t r o u s

second in ex­

anim als,

39.29 i n

a n i m a l s a n d 48 .52

anim als.

T he th y ro id counts p e r

s e c o n d i n E x p e r i m e n t IV (B) w e r e

2 6 .2 4 in t h e p r o e s t r o u s

anim als,

15.49 i n the e s t r o u s

15.64 in t h e m e t e s t r o u s

anim als,

a nd

anim als,

16.76 i n th e d i e s t r o u s

ani­

m als .
When t h y r o id a c tiv ity w as
gram

of t h y r o i d p e r

dose, the data
iodine uptake

expressed as

counts p e r m i l l i ­

s e c o n d o r a s p e r c e n t u p ta k e of th e i n j e c t e d

s h o w e d a h i g h ly s i g n i f i c a n t i n c r e a s e i n r a d i o a c t i v e
o n l y d u r i n g p r o e s t r u s , i n b o th e x p e r i m e n t s .

Body w e ig h ts and th y r o id w e i g h t s .

T h e r e w e r e no s i g ­

n i f i c a n t d i f f e r e n c e s b e t w e e n e i t h e r the bo dy w e i g h t s o r t h y r o i d
w eights

of th e d i f f e r e n t g r o u p s in e i t h e r e x p e r i m e n t .

75
TABLE
I 13 1 U P T A K E

V I (A )

B Y T H E T H Y R O ID G L A N D S O F
ST A G E OF ESTROUS CYCLE

M IC E A T

THE

Body
Wt.

C ts./
Sec.

C ts./
m g ./
s e c ./
100
gm.

22.42
± 0.40*

67.69"
± 4.85

122.04"
± 13.39

1 5 .7 4 "
± 1.13

11.42
± 0.30

8

22.88
± 0.42

39.29
± 3.45

65.43
± 6.08

9.14
± 0.81

11.79
± 0.45

M et­
estrus

13

23.00
± 0 .4 1

39.96
± 2.43

66.03
± 5.00

9.29
± 0.56

11.84
± 0.68

D i­
estru s

17

22.82
± 0.40

48.52'
± 2.98

74.75
± 8.50

10.62
ak 0.66

11.31
± 0.62

S ta ge
of the
Cyc l e

P ro­
estrus
E strus

No.
of
A ni­
m als

12

* S tandard

error.

1 S ignificant a t
" Significant at

5 p e r c e n t level.
1 p e r c e n t le v e l .

Pet.
D o se

T hyroid
m g . / 100
gm.
Body Wt.

76
TABLE
I

131

UPTAKE

No.
of
Ani m als

Stage
of the
C ycle

lo

P ro­
estru s

VI (B )

B Y T H E T H Y R O ID G L A N D S O F M IC E A T
STAG E OF ESTROUS CY CLE

THE

Body
Wt.

C ts./
Sec.

C ts./
m g ./
se c ./
100
gm.

21.69*
± 0 . t>7

26.24"
=fc 1.37

49.12"
± 6.73

23.85"
± 1.24

13.47
± 0.69

23.00
0.57

15.49
± 1.77

21.03
=fa 3.72

14.08
± 1.61

14.81
± 1.29

P et.
Dose

T hyroid
m g./lO O
gm.
Body Wt.

E strus

7

M et­
estru s

8

2 2 .2 5
± 0.61

15.64
db 1.62

23 .90
± 3.69

14.22
± 1.47

14.30
± 1.16

D i­
estru s

19

22.10
± 1.27

16.76
± 1.13

22 .8 4
± 1.99

15 .00
± 1.06

±

* S tandard E r r o r .
"

S ig n ific a n t a t 1 p e r c e n t level.

15.83
0.88

77
E xperim ent V
T h e E f f e c t s of E s t r o g e n a n d P r o g e s t e r o n e on 1*3* U p t a k e b y t h e
T h y r o i d G l a n d of O v a r i e c t o m i z e d R a t s

The follow ing f o u r

experim ents

w e r e p l a n n e d to s tu d y t h e

m e c h a n i s m s i n v o l v e d i n i n d u c i n g a n d c o n t r o l l i n g th e
t i o n s of t h y r o i d a c t i v i t y i n the

cyclic

rat.

E x p e r i m e n t V w a s p l a n n e d to d u p l i c a t e a s n e a r l y
s i b l e th e c h a n g e s i n t h e
the f o u r s t a g e s

gen, p r o g e s te r o n e ,
ovariectom ized

cycle.

and c o m b in a tio n s

rats

as p o s ­

s te rio d h orm o ne balance o c c u rrin g

of t h e e s t r o u s

v aria­

to d e t e r m i n e

r a d io a c tiv e io d in e by the th y ro id .

Physiological doses

during
of e s t r o ­

of t h e m w e r e i n j e c t e d i n t o

th e ir influence
Under these

on t h e u p t a k e of
conditions it was

i m p r a c t i c a l t o u s e n o r m a l c o n t r o l a n i m a l s b e c a u s e of the c y c l i c
v a r i a t i o n of t h e i r

th y ro id activity.

M aterials

F orty
from

fem ale

rats

C arw orth F a r m s ,

they w e r e p u t in

and M e th o d s

w e ig h in g

150 to

180 g r a m s

N e w C ity , N ew Y o r k .

c a g es in an a i r

the t e m p e r a t u r e

of 24 ±

(Hoppert ratio n )

and w a t e r

w ere

At t h e i r

obtain ed

arrival,

conditioned l a b o r a t o r y having

1* C e n t i g r a d e .
ad l i b i t u m .

They w ere

o f f e r e d food

T he a n i m a l s w e r e

78
o v a r i e c t o m i z e d b y u sin g the d o r s a l a p p r o a c h .
d i v i d e d in to s i x g r o u p s

of s i x o r

seven rats

n u m b e re d individually by c o lo rin g them
b od y w i t h p i c r a m i e

T h e y w e r e th e n
in e a c h .

They w e re

in d i f f e r e n t a r e a s of t h e

acid.

F i f t e e n d a y s a f t e r t h e o p e r a t i o n , the a n i m a l s w e r e m a i n ­
t a i n e d on a lo w i o d i n e
w ater.

They w ere

t e s t d i e t ( R e m i n g t o n ) , a n d do ub le d i s t i l l e d

i n j e c t e d i n t r a p e r i t o n e a l l y d a i l y w ith 5 m i c r o -

g r a m s N a l c o n t a i n e d in 0 . 2 m i l l i l i t e r s of do ub le d i s t i l l e d w a t e r f o r
ten d ay s.
The e s t r o g e n u s e d w as e s t r a d i o l b e n z o a te
s o l v e d in p e a n u t o i l .

It w as

orated.

d is­

d i l u t e d in c o r n o il so t h a t 6 r a t - u n i t s

w e r e c o n t a i n e d in 0.1 m i l l i l i t e r of c o r n o il.
d i s s o l v e d in e t h e r ,

(S c h e r in g )

P rogesterone

was

t h e n m i x e d w ith c o r n oil a nd e t h e r w a s e v a p ­

B o t h i n j e c t e d d o s e s of 0 .4 o r

0.8 m illig r a m s w ere

con­

t a i n e d in *0.1 m i l l i l i t e r of c o r n o il.
T w e lv e d a y s a f t e r
w e r e t r e a t e d a s follows:

standardizing

the N a l u p ta k e the a n i m a l s

Group 1 was

kept as control.

Groups

II,

III, an d IV w e r e p r i m e d b y i n j e c t i n g i n t r a p e r i t o n e a l l y 2 r a t - u n i t s of
e stra d io l benzoate
The a n i m a l s

one day b e f o r e

i n j e c t i n g the 6 r a t - u n i t s .

in G r o u p II w e r e

injected

i n t r a p e r i o t o n e a l l y w ith

6 r a t - u n i t s of e s t r a d i o l b e n z o a t e f o r t y - e i g h t h o u r s b e f o r e a u t o p s y .

79
G r o u p s III an d IV w e r e i n j e c t e d f i r s t w ith 6 r a t - u n i t s
benzoate

s e v e n t y - t w o h o u r s b e f o r e b e in g

of e s t r a d i o l

sacrificed.

They w ere

a l s o i n j e c t e d on t h e n e x t d a y w it h 0.4 and 0.8 m i l l i g r a m s p r o ­
gesterone

respectively.

The

a n i m a l s in G r o u p s

0.8 m i l l i g r a m s

progesterone,

V a n d VI w e r e i n j e c t e d w ith 0.4 a nd
respectively, fo rty -eig h t hours before

autopsy.
A ll a n i m a l s

w ere

of 1*^* c o n t a i n e d in

i n j e c t e d i n t r a p e r i t o n e a l l y w ith

1 m i l l i l i t e r of s a l i n e

1 m icrocurie

solution six h o u rs b e fo re

being s a c rific e d .
The
dissected,

anim als w ere
cleaned

then s a c rific e d , th e ir thyroid glands w ere

carefully,

w e ig h e d on a t o r s i o n b a l a n c e ,

p l a c e d in th e c e n t e r of m e t a l d i s c s .

an d

T he t h y r o i d g l a n d s w e r e

t h e n d r i e d f o r t w e l v e h o u r s in an o v e n a d j u s t e d a t th e t e m p e r a t u r e
of 90°
th e d r y

C entigrade.

T h e t h y r o i d u p t a k e w a s m e a s u r e d by c o u n t i ng

t h y r o i d s by t h e u s e of a G e i g e r C o u n t e r .

Re s u i t s
1 31
I______u
ptake.
of e s t r a d i o l b e n z o a t e

F o rty -eig h t hours

a fte r injecting

th e t h y r o i d u p ta k e of I

h i g h e r t h a n t h a t of th e

control.

was

6 rat-units
significantly

When 0.4 m i l l i g r a m s

of p r o g e s t e r o n e

80
was injected,

e i t h e r alone

o r tw enty-four hours after 6 ra t-u n its

of e s t r a d i o l b e n z o a t e t h e f o r t y - e i g h t h o u r u p ta k e of I
creased

was d e ­

s i g n i f i c a n t l y w h e n c o m p a r e d to t h a t of the c o n t r o l g r o u p .
In r a t s

m illigram s

in j e c t e d with 6 u n its

of p r o g e s t e r o n e

u p t a k e of 1 * ^

did n o t d if f e r

F o rty -e ig h t hours
gesterone

th e 1 ^ ^

The
was

131

of e s t r a d i o l f o llo w e d by 0.8

tw enty-four hours later,

the

six-hour

s i g n i f i c a n t l y f r o m t h a t of the c o n t r o l .

afte r injecting

0.8 m i l l i g r a m s

uptake was i n c r e a s e d

counts p e r th y ro id p e r

of p r o ­

significantly.

s e c o n d of the c o n t r o l g r o u p

5 6 . 0 7 c o m p a r e d to 67.61 of th e g r o u p i n j e c t e d w ith 6 r a t -

u n i t s of e s t r a d i o l b e n z o a t e .
j e c t e d w i th 6 r a t - u n i t s
m illig ram s
second,

w i t h 0 . 4 an d
counts p e r

reg istered

46 .22 a n d 53.08 c o u n t s p e r

progesterone

sh ow ed 41.55 and 61.21

respectively.

S i m i l a r d i f f e r e n c e s w e r e fou nd when the v a l u e s w e r e
puted a s
weight o r

0.8

T h e t h y r o i d g l a n d s of the g r o u p s i n j e c t e d

0.8 m i l l i g r a m s

second,

t h y r o i d g l a n d s of th e g r o u p s i n ­

e s t r a d i o l b e n z o a t e fo llow e d by 0.4 o r

progesterone

respectively.

The

counts p e r m i l l i g r a m

of t h y r o i d p e r

a s p e r c e n t of i n j e c t e d d o s e .

com ­

100 g r a m s bo dy

81
TABLE

V II

T H E E F F E C T S O F E S T R O G E N AND P R O G E S T E R O N E ON I 131
U P T A K E BY T H E T H Y R O ID G L A N D OF
O V A R I E C T O M I Z E D RA TS
G roup
No.

T reatm ent

B od y Wt.

Spayed c o n tro ls

220.33
± 5.41*

Spayed + 6 r a t- u n its
E s tra d io l B enzoate

214 .33
* 9 .8 4

III

Spayed + 6 r a t- u n its
E s tr a d io l B enzoate +
0 .4 m g . p r o g e s t e r o n e

22 3 .8 6
db 7.04

IV

Spayed + 6 r a t - u n its
E s tra d io l B enzoate +
0.8 m g . p r o g e s t e r o n e

2 0 9 .1 7 '
± 4.59

S p a y e d + 0 .4 m g
p rogesterone

221.11
± 7.98

S p a y e d ± 0.8 m g
progesterone

2 2 9 .8 6
± 8 .3 7

II

VI

* Standard e r r o r .
1 S i g n i f i c a n t a t 5 p e r c e n t le v e l.
'' S i g n i f i c a n t a t

I

N o. of
A nim als

1 p e r c e n t le v e l.

82

TABLE
C ts./S e c ./
Thyroid

C ts./m g ./
100/Sec.

V II ( C o n t i n u e d )
P et.
Dose

T h yroid/
100

6.60

T hyroid
Wt. ( d ry )

56.0 7
± 5.96

1.75
± 0. 20

13.91
± 0.47

±

0.46

3.27
± 0.17

6 7 .0 1 '
± 9.93

2.25*
± 0.40

16 .78 '
± 0.87

6.96
± 0.36

3.07
± 0.45

4 6.22”
± 2.22

1.07
± 0.24

11.47
± 0.56

7.63
± 0.62

3.23
± 0.77

5 3 .0 4
± 3.9 9

1.81
± 0.25

13.16
± 0.98

6.87
± 0.33

2.97
± 0.14

4 1 .5 5 ''
± 3.05

1 03
± 0.25

10.31
± 0.75

5.59
± 0.41

2.68
± 0.25

6 1 .2 1 '
± 3.94

1.88
± 0.17

15.19'

6.17
± 0.39

3.28
± 0.89

±

0.68

83
Body and th y ro id w e ig h ts .

T h e r e w e r e no s i g n i f i c a n t d i f ­

f e r e n c e s b e t w e e n t h e b o d y w e i g h t s o r t h y r o i d w e i g h t s of an y of
t he g r o u p s .

84
E x p e r i m e n t VI
T h e E f f e c t of E s t r o g e n o n 1*3* U p ta k e by th e T h y r o i d G l a n d s of
O v a r ie c to m iz e d and O v a rie c to m iz e d , A d re n a le c to m iz e d R ats

M aterials

a nd M e t h o d s

F o r ty - e ig h t adult fem ale
w e re u se d in this
F arm s,

experim ent.

N ew C i t y , N e w Y o r k .

rats

w e ig h in g 210 to 250 g r a m s

They w e re

supplied by C a r w o r th

T w e n t y - f o u r of t h e s e

o v a r i e c t o m i z e d , t h e n d i v i d e d in to t h r e e g r o u p s - - I ,

rats

w ere

II, and I I I - - w i t h

eight a n im a ls in each group.
The o ther
alectom ized,

tw enty-four

rats

w ere

t h e n d i v i d e d i nto t h r e e

o v a r i e c t o m i z e d and a d r e n ­

groups--IV ,

V, a n d VI.

B ot h

o p e r a t i o n s w e r e p e r f o r m e d by the d o r s a l a p p r o a c h .
The

rats

w ere

a l l o t t e d to g r o u p s f o u r d a y s a f t e r the o p e r ­

a tio n and m a i n t a i n e d on t h e i r

specified e x p e rim en ta l tr e a tm e n t for

tw enty-one days.
T o p e r m i t s t a n d a r d i z i n g th e i o d i n e i n t a k e ,
f e d a n i o d i n e d e f i c i e n t d i e t ( R e m i n g t o n d ie t) .
rats

all groups w ere

The a d re n a le c to m iz e d

w e r e m a i n t a i n e d on 1 p e r c e n t N a C l i n do u b le d i s t i l l e d w a t e r ,

w h i le th e r e s t w e r e m a i n t a i n e d on d o u b le d i s t i l l e d w a t e r .

85
The s o d i u m c h l o r i d e w a s a n a l y z e d f o r
m e t h o d of M c C u l l a g h (1934).

The l o t of s a l t

c o n t a i n e d 0 .3 6 m i c r o g r a m s of
a l e n t to 0.85 m i c r o g r a m s

per gram

N a l.

c o n t a i n e d 0.21 m i c r o g r a m s Na l.

ix se d

of

The a v e r a g e

s u m p t i o n of the a d r e n a l e c t o m i z e d

io d in e

(B a k e r C. P.)

s a lt,

which w as e q u i v ­

d a ily

ra t was a b o u t

co n ten t by the

salt w ater con­

2 5 m illiliters,

It w as

then

n ecessary

to the w a t e r of th e n o n a d r e n a l e c t o m i z e d

rats

s o

w hic h

to add Nal

t h a t they i n g e s t e d

the s a m e a m o u n t of Nal in t h e i r d r in k in g w a t e x*.
The a n i m a l s w e r e a l s o
5 m icrogram s

i n je c te d i n t r a p e r i t o n e a l l y

of Nal c o n t a i n e d in 0.2 m i l l i l i t e r s

daily with

of double d i s t i l l e d

w ater.
E s tr a d io l benzoate

(Sc hering) w as d i s s o l v e d

It w a s d i lu te d with c o r n o i l so th a t e i t h e r

6

u ni ts of it w e r e c o n t a i n e d in 0.1 m i l l i l i t e r

of

The r a t s

in g r o u p s I a nd IV w e r e

r a . t —u n it s o r 300 r a t c o rn

used

s la

i n j e c t e d i n t r a p e r i t o n e a l l y with 0.1 m i l l i l i t e r o f
a nd V w e r e

i n j e c t e d i n t r a p e r i t o n e a l l y w ith 4

in pe a n u t oil.

oil.
c o n t r o l s and w e r e

corn

oil.

ra t-u n its

b e n z o a t e a t 6 - d a y i n t e r v a l s to s i m u l a t e a s p o n t a n e o u s
F o r t y - e i g h t h o u r s b e f o r e e n d i ng the e x p e r i m e n t
i n t r a p e r i t o n e a l l y with 6 r a t - u n i t s of e s t r a d i o l

G r o u p s II

of e s t r a d i o l
e s tr o u s cycle.

t h e y w e r e in j e c t e d

b en zo ate.

86
T h e a n i m a l s i n G r o u p s III a n d VI w e r e i n j e c t e d i n t r a p e r i ­
t o n e a l l y w i t h 300 r a t - u n i t s
f o r tw e n t y d a y s .

of e s t r a d i o l b e n z o a t e e v e r y o t h e r d a y

The l a s t in je c tio n w as given fo rty -e ig h t h o u r s

b e f o r e en d in g t h e e x p e r i m e n t .
A ll r a t s w e r e t h e n i n j e c t e d w i t h 0.5 m i c r o c u r i e of I
six h o u rs b e fo re autopsy.

Four

an im a ls w ere injected at a tim e

w ith a f i v e - m i n u t e i n t e r v a l b e tw e e n in je c tio n t i m e s .
w ere

th e n k i l l e d w i t h e t h e r ,

131

The a n im als

th e ir th y ro id glands d is s e c te d ,
*

c l e a n e d c a r e f u l l y , w e i g h e d on a t o r s i o n b a l a n c e ,
t h e c e n t e r of m e t a l d i s c s .

and p l a c e d i n

T h e t h y r o i d s w e r e t h e n d r i e d by l e a v ­

i n g t h e m f o r t w e l v e h o u r s i n a n o v e n h a v i n g the t e m p e r a t u r e of
90* C e n t i g r a d e .

They w e re

a t a f ix e d g e o m e t r y to i t s

c o u n t e d by the u s e of a G e i g e r C o u n t e r

end-w indow .

w e i g h e d on a t o r s i o n b a l a n c e .
th eir ad ren als in tact w ere

T he p i t u i t a r y g l a n d s w e r e

T h e a d r e n a l s of th e r a t s

t h a t ha d

a l s o w e ig h e d .

R esults

I

13 1

uptake.

tra d ia l benzoate

The

spayed,

adrenalectom ized ra ts

given e s -

* T131

s h o w e d a s i g n i f i c a n t i n c r e a s e in th e u p t a k e of I

by t h e i r g l a n d s w h e n c o m p a r e d to t h e i r

control.

The t h y r o i d u p -

| 41
t a k e of I

of t h e

spayed a d re n ale c to m iz e d

r a ts was

significantly

87
l e s s th a n th a t of th e r a t s

that w ere

s p a y e d o n ly .

T here is

also a

s t a t i s t i c a l l y s i g n i f i c a n t i n c r e a s e i n th e u p t a k e of the th y r o i d

of a d -

ren alectom ized

when

rats

g i v e n 6 r a t - u n i t s of e s t r a d i o l b e n z o a t e ,

c o m p a r e d to t h e u p t a k e of th e r a t s
r e c e i v e d th e

that w ere

s p a y e d only, a n d

sam e treatm en t.

T h o u g h t h e i n c r e a s e in t h e u p t a k e of th e
tom ized ra ts

spayed,

t r e a t e d w i t h t e n d o s e s of 300 r a t - u n i t s

b en z o ate in je c te d e v e ry o th e r day w as
u p t a k e b y t h e t h y r o i d s of s p a y e d r a t s

of e s t r a d i o l

s i g n i f i c a n t l y l e s s t h a n t he
t r e a t e d the

it was

s i g n i f i c a n t l y h i g h e r th a n i t s ow n c o n t r o l .

i n the

case

of s p a y e d r a t s .

adrenalec-

The counts p e r

s a m e w ay , y e t
T his w as not tru e

s e c o n d p e r t h y r o i d of

th e s p a y e d g r o u p w hich w as in j e c t e d w ith 6 r a t - u n i t s

an d t h e

o t h e r g r o u p t h a t w a s g i v e n t e n i n j e c t i o n s of 300 r a t - u n i t s
diol b e n z o ate, w e r e

4 5 . 9 9 a n d 42.49,

t h e i r c o n tro l w hich w as

3 9.98 ( T a b l e VIII).

in je c te d w ith 6 r a t - u n i t s
h ig h e r uptake than the
The counts p e r
ad renalecto m ized

rats,

respectively,

estra­

c o m p a r e d to

G r o u p s II w h i c h w a s

of e s t r a d i o l b e n z o a t e h a d a s i g n i f i c a n t l y

spayed c o n tro l group.
s e c o n d p e r t h y r o i d of th e
given 6 r a t - u n i t s

and th o se given ten in je c tio n s

spayed and

of e s t r a d i o l b e n z o a t e ,

of 300 r a t - u n i t s

of e s t r a d i o l b e n z o a t e

88
TABLE

V III

T H E E F F E C T O F E S T R O G E N ON I 131 U P T A K E BY T H E T H Y •
R O I D G L A N D S O F O V A R I E C T O M I Z E D AND O V A R I E C T O M I Z E E
A D R E N A L E X T O M IZ E D RATS

C ts./se c .
T hyroid

C ts./m g .
100 gm,

Spayed C o n tro l

39.98'
± 1.77

1.02
± 0.12

Spayed ± 6 r a t- u n its
e s tr a d io l b en zo ate killed
a f t e r 48 h o u r s

45 99'
± 181

1.00
± 0.20

III

S p a y e d ± 300 r a t - u n i t s
e s tra d io l benzoate in jected
e v e r y o t h e r d a y (10 d o s e s )

42 49
± 1.98

1 10
± 0.14

IV

Spayed and A d r e n a le c to m iz e d
control

29-96"
± 1.61

0.80
± 0.26

V

Spayed and A d r e n a le c to m iz e d
+ 6 ra t-u n its estradiol b en ­
zoate

54.47"
± 1.89

1.11
± 0.14

VI

Spayed and A d r e n a le c to m iz e d
± 300 r a t - u n i t s e s t r a d i o l
b e n z o a t e (10 d o s e s )

3 5 .6 9 '
± 3.22

0.86
± 0.10

G roups

T reatm ent

I

II

* Standard

error.

1 Significant at 5 p e r c e n t level when c o m p a r e d

to i t s

co:

trol.
"
+i*r>1

Significant at

1 p e r c e n t le v e l when c o m p a r e d

to i t s

cc

89

TABLE

T h y r o i d / 100
D

w

15.03

B o d y Wt.

V III ( C o n t i n u e d )

T hyroid
w -

<d r y7)

P itu itary /

A drenal/

100

100

=fc 0.24

4.77
± 0.40

15.82
± 1.70

0.68

6.42
± 0.39

3.25
± 0.20

5.42
± j . 30

20.17*
± 0 .9 4

15.97
± 0.75

7.37'
± 0 .1 6

3.21
± 0. 20

5.83
± 0.10

24.
’'
± 2 .09

11.2 6 "
± 0.61

7.17
± 0 .5 0

3.15
± 0.24

4.37
± 0.33

20.48"
± 0.96

8.05'
± 0.45

4.03
± 0.32

5. lt>
± 0.20

13.42
± 1.22

8.1 3 ’
± 0 .5 0

3.20
=fc 0.24

5.9 7'
± 0.14

±

0.66

17.69 '
±

5.8 5
± 0.21

2.88

90
w ere

5 4.4 7 an d 3 5 . 6 9 c o m p a r e d to t h e i r a d r e n a l e c t o m i z e d c o n t r o l

w hi c h w a s

29.96.

W h en t h y r o i d a c t i v i t y w a s e x p r e s s e d a s c o u n ts p e r m i l l i ­
gram

of t h y r o i d p e r

100 g r a m s b o d y w e ig h t, no s i g n i f i c a n t d i f f e r ­

e n c e s b e t w e e n t h e v a r i o u s g r o u p s w a s found.
The counts p e r m i l l i g r a m
w e i g h t of t h e

spayed r a ts

thyroid p e r

given 6 r a t - u n i t s

t h o s e g i v e n t e n d o s e s of 300 r a t - u n i t s
1.00 a n d
was

1.10, r e s p e c t i v e l y ,

1.02.

The

aged

e s tra d io l benzoate and

of e s t r a d i o l b e n z o a t e w e r e

c o m p a r e d w ith t h e i r

c o n t r o l w h ic h

s p a y e d a d r e n a l e c t o m i z e d r a t s g iv e n 6 r a t - u n i t s

a n d t h o s e g i v e n t e n d o s e s of 300 r a t - u n i t s
c o u n te d

100 g r a m s body

e s tr a d io l benzoate

1.11 a n d 0 .86, c o m p a r e d to t h e i r own c o n t r o l w h ic h a v e r ­

0.80 c o u n t s p e r m i l l i g r a m

thyroid p e r

Wh en t h e t h y r o i d a c t i v i t y w a s
c e n t u p t a k e of t h e i n j e c t e d d o s e of 1
c o n tr o ls fixed
r a t - u n i t s fixed
300 r a t - u n i t s

e x p r e s s e d in t e r m s
131

of p e r -

, the t h y r o i d s of the s p a y e d

15.03 p e r c e n t of the d o s e ,

the s p a y e d r a t s g iv e n 6

17.96 p e r c e n t of the d o s e , the s p a y e d r a t s

given

of e s t r a d i o l b e n z o a t e e v e r y o t h e r day f o r twe nt y d a y s

fixe d

15.97 p e r c e n t .

1 1 . 2 6

p e r c e n t of th e d o s e , w hile the

ra ts that w ere

100 g r a m s body w e i g h t .

The

spayed, a d re n ale c to m iz e d

given 6 r a t - u n i t s

c o n t r o l s fi x e d

s p a y e d and a d r e n a l e c t o m i z e d

of e s t r a d i o l b e n z o a t e fixe d 20.48

91
p e r c e n t o f th e d o s e
w e re g iv e n

and th e

300 r a t - u n i t s

every

13.42 p e r c e n t of th e d o s e .
6 ra t-u n its
in je c te d 1

sp a y ed and a d r e n a le c to m iz e d

ra ts

o t h e r d a y f o r tw e n ty d a y s f i x e d

T h e t h y r o i d s of t h e s p a y e d r a t s

o f e s t r a d i o l b e n z o a t e f ix e d a h i g h e r p e r c e n t a g e

131

sig n ific a n t.

th a n th e ir

c o n tro l.

ra ts

g iv e n 6 r a t - u n i t s

t h a n th e

Body w e ig h ts .
u n its

of e s t r a d i o l w as

tro ls,
w as

spayed r a ts

t r e a t e d th e

T h e g a i n by th e

spayed,

sam e

spayed r a ts

sig n ifi­

w ay.

g iv e n 6 r a t -

s i g n i f i c a n t l y h i g h e r t h a n t h a t of t h e i r

con­

w h i le th e g a in o f t h o s e g iv e n th e l a r g e r d o s e o f e s t r o g e n

sig n ific a n tly le s s

t h a n t h a t of t h e i r

T he a d re n a le c to m iz e d
g en l o s t w eig h t.
p e rim e n t w ere
in

o f th e

of e s t r a d i o l b e n z o a t e w a s

s i g n i f i c a n t l y h i g h e r t h a n b o th th e c o n t r o l g r o u p s a n d a l s o
ca n tly h ig h e r

g iv e n

T h i s i n c r e a s e i n th e u p t a k e w a s

S t i l l th e p e r c e n t u p ta k e b y th e t h y r o i d of th e

a d re n a le c to m iz e d

th at

spayed

ra ts

g iv e n th e l a r g e

dose

of e s t r o ­

T h e a v e r a g e b o d y w e i g h t s a t th e e n d o f th e e x ­
2 6 9 .6 g r a m s i n th e s p a y e d c o n t r o l s ,

r a t s g iv e n 6 r a t - u n i t s

in th e c a s e

c o n tro ls.

of sp ay ed r a t s

2 6 4 .5 g r a m s

of e s t r a d i o l b e n z o a t e ,

g iv e n te n d o s e s o f 300 r a t - u n i t s

e s t r a d i o l b e n z o a t e e v e r y o t h e r d a y , 2 2 6 .5 g r a m s f o r
re n a le c to m iz e d c o n tro ls,
a d re n a le c to m iz e d r a ts

2 3 3 .0 g r a m s

2 3 7 .2 5 g r a m s i n th e c a s e

of

spayed a d ­

of th e

spayed,

g iv e n 6 r a t —
u n i t s of e s t r a d i o l b e n z o a t e and

92
TABLE

IX

I N F L U E N C T O F E S T R O G E N ON BODY W E IG H T GAINS AND
F O O D AND W A T E R C O N S U M P T IO N O F O V A R IE C T O M I Z E D AND O V A R IE C T O M IZ E D , A D R E N ­
A L E C T O M IZ E D RATS

G roup
No.

N um ber
of
A n im als

T re atm en t

8

Spayed c o n tro l

I

Spayed + 6 r a t- u n its e s tr a d io l
b e n z o a t e k i l l e d a f t e r 48 h o u r s

II

III

S p a y e d + 300 r a t - u n i t s e s t r a d i o l
b e n z o a t e e v e r y o t h e r d a y (10
doses)

8

IV

S payed and a d r e n a le c to m iz e d
c o n tro l

8

\r

S payed and a d r e n a le c to m iz e d
r a t - u n i t s e s tr a d io l b e n z o ate

V

+■ 6

8

Spayed and a d re n a le c to m iz e d +
300 r a t - u n i t s e s t r a d i o l b e n z o a t e
e v e r y o t h e r d a y (10 d o s e s )

VI

**
4

-=3s---:
* S ta n d a rd

erro r.

' S i g n i f i c a n t a t 5 p e r c e n t l e v e l w h e n c o m p a r e d to i t s
''

I

S ig n ific a n t a t

1 p e r c e n t l e v e l w h e n c o m p a r e d to i t s

cont
cor

93

T A B L E IX (C ontinued)

I n itia l
B od y
wt

2 3 3 .6 2
9 .7 3

F in a l
B od y
Wt

269.62

C hanges
in Body
wt

_
Food
C o n s u m p tio n
p e r A n im a l
p e r D ay

W a ter
C o n su m p tio n
p e r A n im a l
p e r D ay

1 3 .1 7

2 8 .1 7

± 3.91

2 3 .5 0
± 3 .9 2

2 3 3 .0 0
± 7.42

2 6 4 .5 0
± 3.23

3 1 .0 0 '
± 3 .52

1 5.17

16.83

2 1 7 .7 5
± 6 .4 9

2 3 3 .0 0
± 6 .1 5

12.00

15.88

2 1 6 .0 0
± 4 .8 0

2 2 6 .5 0
± 2 .9 0

1 0 .5 0
± 6 .7 6

1 1.67

2 7 .8 3

2 2 6 .5 0
± 7 .1 4

2 3 7 .2 5
± 2 .4 7

1 0.75
± 3 .3 7

11.88

2 2 .5 0

2 3 0 .0 0
± 7 .9 7

2 2 1 .2 8
± 4 .6 6

-6 .2 8 ”
± 5 .5 0

1 0 .9 0

16.83

1 6 .0 0 '
± 5.83

94
2 2 1 .28 g r a m s i n t h e c a s e o f s p a y e d , a d r e n a l e c t o m i z e d r a t s
t e n d o s e s o f 300 r a t - u n i t s
The
ra ts

t r e a t e d w ith 6 r a t - u n i t s

day g a in e d
g a in e d

b e n z o ate

The

w h ile t h e

ra ts

c o n tro ls

spayed, a d re n a le c to m iz e d r a ts
10.7 g r a m s and th e

g iv e n
spayed,

of 300 r a t - u n i t s o f e s t r a d i o l

l o s t 6.3 g r a m s .

W h en e x p r e s s e d i n m i l l i g r a m s p e r

b o d y w e i g h t th e t h y r o i d s o f th e s p a y e d c o n t r o l s ,

g iv e n 6 r a t - u n i t s

doses

e v e ry o th e r

spayed, a d re n a le c to m iz e d

g iv e n t e n d o s e s

T h y ro id w e ig h ts .
gram s

spayed

e s t r a d i o l b e n z o a t e g a i n e d 3 1 .0 g r a m s

of e s t r a d i o l b e n z o a t e g a i n e d

a d re n a le c to m iz e d

w h ile th e

g i v e n t e n d o s e s of 300 r a t - u n i t s

1 6 .0 g r a m s .

10.5 g r a m s ,

6 ra t-u n its

ra ts

of e s t r a d i o l b e n z o a te e v e r y o th e r day.

s p a y e d c o n t r o l s g a i n e d 2 3.5 g r a m s ,

a n d th e s p a y e d r a t s

g iv e n

of 300 r a t - u n i t s

m illig ra m s,

100

th e s p a y e d

o f e s t r a d i o l b e n z o a t e a n d t h o s e g iv e n t e n
e v e ry o th e r day w e re

a n d 7.37 m i l l i g r a m s ,

5.85 m i l l i g r a m s ,

re sp e ctiv ely .

6 .42

T he th y r o id s of

th e g r o u p t r e a t e d w ith th e l a r g e d o s e o f e s t r o g e n

show ed a s i g ­

n i f i c a n t i n c r e a s e i n w e i g h t a b o v e t h e i r ’ c o n t r o l g r o u p , due to t h e
l i g h t e r w e i g h t of th e c o n t r o l a n i m a l s .
e x p r e s s e d in th e

sa m e w ay w e re

a d re n a le c to m iz e d

ra ts,

to m iz e d

ra ts

T h e t h y r o i d w e ig h ts w h e n

7 .1 7 m i l l i g r a m s f o r th e s p a y e d

8 .0 5 m i l l i g r a m s f o r th e

g iv e n 6 r a t - u n i t s

spayed a d r e n a le c ­

of e s t r o g e n a n d 8 .1 3 m i l l i g r a m s

95
f o r th e

spayed a d re n a le c to m iz e d r a ts

u n i t s of e s t r o g e n

ev ery

o t h e r d ay .

P itu ita ry w e ig h ts .
b e tw e e n th e p i t u i t a r y
to m ized a n im a ls

of e s t r a d i o l b e n z o a t e
g ram s

body w e ig h t,

T h e r e w e r e no s i g n i f i c a n t d i f f e r e n c e s

w eig h ts.

g iv e n

a n im a ls

T h e p i t u i t a r i e s of th e o v a r i e c -

6 ra t-u n its,

a n d t h o s e g iv e n 300 r a t - u n i t s

w e ig h e d 5.42 a n d 5.83 m i l l i g r a m s p e r
re s p e c tiv e ly ,

w e ig h e d 4 .7 7 m i l l i g r a m s .
b e tw e en th e m .

g iv e n te n d o s e s of 300 r a t -

T here

c o m p a r e d to t h e i r

d io l b e n z o a t e w e i g h e d

c o n t r o l w h ic h

w e r e no s i g n i f i c a n t d i f f e r e n c e s

T h e p i t u i t a r i e s of o v a r i e c t o m i z e d ,

g iv e n 6 r a t - u n i t s

100

a d re n a le c to m iz e d

and th o s e g iv e n 300 r a t - u n i t s

5 .1 6 and 5.97 m i l l i g r a m s p e r

of e s t r a ­

100 g r a m s

b od y w e ig h t c o m p a r e d to t h e i r c o n t r o l w e ig h t o f 4.37 .

A d ren al w e ig h ts .
w ith e s t r a d i o l b e n z o a t e
th e ir

c o n tro ls.

The

u n i ts

of t h e

w ere

s i g n i f i c a n t l y h e a v i e r t h a n t h o s e of

a d r e n a l w e ig h ts of th e g r o u p t r e a t e d w ith t e n

d o s e s o f 300 r a t - u n i t s
th a n t h o s e

T he a d r e n a l w e ig h ts o f b o th g r o u p s t r e a t e d

g rou p

on a l t e r n a t e

days w e re

s ig n ific a n tly h e a v ie r

t r e a t e d w ith th e s in g le i n j e c t i o n of 6 r a t -

of e s t r a d i o l b e n z o a t e .
T h e a d r e n a l w e i g h t s of the o v a r i e c t o m i z e d a n i m a l s g iv e n a

s in g le i n j e c t i o n of 6 r a t - u n i t s ,

a n d t h o s e g iv e n te n i n j e c t i o n s

of 300

96
ra t-u n its
per

of e s tr a d io l b en zo ate w e re

100 g r a m s

2 0 .1 7 a n d 2 4 .45 m i l l i g r a m s

b o d y w e i g h t c o m p a r e d to t h e i r c o n t r o l ' s w e ig h t of

15.82.
T h e f o l lo w in g

sig n ific a n t fa c ts

a r e b r o u g h t to l i g h t b y t h i s

e x p e rim e n t:
1.

T h e io d in e

u p ta k e o f t h e t h y r o i d s of s p a y e d r a t s w a s

s i g n i f i c a n t l y i n c r e a s e d b y a s m a l l d o s e of e s t r o g e n g i v e n f o r a
s h o r t p e rio d , b u t n o t by a la r g e
2.

T h y r o i d i o d i n e u p ta k e of th e s p a y e d r a t i s

by a d r e n a l e c t o m y .
th e

d o s e g iv e n c o n t in u o u s ly .

H o w ever,

r e m o v a l of th e a d r e n a l i n c r e a s e s

r e s p o n s e o f th e t h y r o i d of s p a y e d r a t s

c r e a s e in io d in e u p ta k e i s
dosage

A d re n a l w e ig h ts

c r e a s e d w ith e i t h e r

to e s t r o g e n .

g r e a t e r w ith a s m a l l ,

e s t r o g e n t h a n w ith a l a r g e
3.

d ep ressed

The i n ­

sh o rt-te rm

ch ro n ic d osage.

of s p a y e d r a t s

w ere

sig n ific a n tly i n ­

a l a r g e o r a s m a l l d o s e of e s t r o g e n .

97
E x p e r i m e n t VII
T h e E f f e c t s of E s t r o g e n a n d P r o g e s t e r o n e on 1*3* U p ta k e b y
th e T h y r o i d G la n d s of H y p o p h y s e c t o m i z e d - Q v a r i e c t o m i z e d
and O v a rie c to m iz e d R a ts

M a te ria ls

a n d M e th o d s

F o rty h y p o p h y se c to m iz e d -o v a rie c to m iz e d
fe m ale

ra ts,

and fo rty

r a t s w ith a n a v e r a g e b o d y w e ig h t of 150 g r a m s w e r e p u r ­

chased fro m

th e H o r m o n e A s s a y L a b o r a t o r i e s ,

d a y a f t e r t h e i r a r r i v a l th e n o r m a l
u s in g th e d o r s a l a p p r o a c h .
g r o u p s w ith e i g h t r a t s

O n th e

r a ts w e re o v a rie cto m iz e d ,

T he a n i m a l s w e r e d iv id e d into te n

in e a c h .

io d in e t e s t d i e t (R e m in g to n ) ,

C h ic a g o .

T h e y w e r e m a i n t a i n e d on a lo w

cmd d i s t i l l e d w a t e r .

The r a t s w e re

i n j e c t e d d a il y d u r i n g th e f o u r t e e n d a y s of th e e x p e r i m e n t w ith 5
m ic ro g ra m s

of N a l.

E s t r a d i o l b e n z o a t e ( S c h e r in g ) w a s
p e a n u t o il.

I t w a s d i lu te d by u s i n g

a m o u n t w a s a lw a y s
P ro g e ste ro n e

c o n ta i n e d in

co rn

s u p p lie d d i s s o l v e d in
o il so t h a t th e i n j e c t e d

0.1 m i l l i l i t e r s .

w a s f i r s t d i s s o l v e d in e t h e r , th e n m ix e d w ith

c o r n o il a n d th e e t h e r w a s e v a p o r a t e d b y a n a i r
j e c t e d d o s e of p r o g e s t e r o n e w a s a l w a y s

c u rre n t.

c o n ta in e d in

The i n ­

0.1 m i l l i l i t e r

of c o r n o il.

I

98
A ll in je c tio n m a t e r i a l s

w e re a d m in iste re d fo rty -e ig h t h o u rs

b e f o r e a u to p sy .
G r o u p s I, II, III, IV , a n d V w e r e th e h y p o p h y s e c t o m i z e d o v a rie c to m iz e d

ra ts.

G roups

VI, VII, VIII, IX, a n d X w e r e

o v a ri­

e c t o m i z e d o n ly .
T w e lv e d a y s a f t e r h y p o p h y s e c t o m y o p e r a t i o n s
tre a te d
tro ls ;

in th e f o llo w in g w a y .
th e y w e re

G r o u p s I a n d VI w e r e

th e

ra ts

used as

w ere
con­

i n j e c t e d i n t r a p e ri to n e a l l y w ith 0 .1 m i l l i l i t e r of c o r n

o i l.
G r o u p s II an d VII w e r e i n j e c t e d w ith 6 r a t - u n i t s
b en zo ate.

G r o u p s III a n d VIII w e r e i n j e c t e d w ith

e s tr a d io l b en zo ate.
gram s

The

300 r a t - u n i t s

of

G r o u p s IV a n d IX w e r e i n j e c t e d w ith 0.2 m i l l i ­

of p r o g e s t e r o n e .

m illig ra m s

of e s t r a d i o l

G ro u p s V and X w e re

i n j e c t e d w ith 0 .4

of p r o g e s t e r o n e .
ra ts

w e r e t h e n i n j e c t e d w ith 3 m i c r o c u r i e

of I

F o u r a n i m a l s w e r e i n j e c t e d a t a t i m e w ith f i v e - m i n u t e i n t e r v a l s
b etw een in je c tio n s .
S ix h o u r s
h ours
w ere

a f te r in je c tin g I

a f t e r in je c tin g
sa c rific e d .

, w h ic h w a s a l s o f o r t y - e i g h t

w ith e s t r o g e n o r p r o g e s t e r o n e ,

The th y ro id

th e a n i m a l s

g la n d s w e r e d i s s e c t e d , c l e a n e d

c a r e f u l l y , w e ig h e d on a t o r s i o n b a l a n c e a n d p l a c e d in the c e n t e r

99
of m e t a l d i s c s .

T h e y w e r e d r i e d b y l e a v in g t h e m f o r tw e lv e h o u r s

in a n o v e n a d j u s t e d a t th e t e m p e r a t u r e
th y ro id s w e re

c o u n te d a t a f i x e d g e o m e t r y f r o m

of a G e i g e r C o u n t e r .
so rb er

of 90* C e n t i g r a d e .

It w as n e c e s s a ry

of 59.2 m i l l i g r a m s p e r

cm

2

to u s e

The

th e e n d w indow
an a lu m in u m a b -

to m a k e i t p o s s i b l e

to c o u n t

th e h ig h l y a c t i v e t h y r o i d s o f th e g r o u p s t h a t h a d t h e i r h y p o p h y s is
in ta c t.

W ith th e u s e

of t h i s a b s o r b e r o n ly

o r i g i n a l c o u n ts w e r e d e t e c t e d .
th e

c o u n ts b a c k to

T h i s m a d e i t n e c e s s a r y to c o r r e c t

100 p e r c e n t in o r d e r to c o m p a r e

h y p o p h y se c to m iz ed

ra ts

The p itu ita rie s
a d re n a ls

13 .37 p e r c e n t o f th e

h a v in g t h y r o i d s

th em

w ith t h e

of low a c t i v i t y .

of th e n o n h y p o p h y s e c t o m i z e d r a t s

and a ll

w e r e w e ig h e d .

R e su lts

1*^* u p t a k e .
th e I

131

T here

w e r e no s i g n i f i c a n t d i f f e r e n c e s b e t w e e n

u p t a k e s by th e . t h y r o i d g l a n d s of th e h y p o p h y s e c t o m i z e d -

o v a rie c to m iz e d r a ts ,
of 0.4 m i l l i g r a m s

e x c e p t in G r o u p V, w h ic h w a s g iv e n a d o s e

p ro g e ste ro n e .

T h is g roup

s i g n i f i c a n t d e c r e a s e i n i t s u p ta k e of I
ow n c o n t r o l .
as

Such d if f e r e n c e s w e re

to ta l th y ro id

show ed a s t a tis tic a lly

w hen c o m p a r e d to i t s

s i g n i f i c a n t o n ly w hen e x p r e s s e d

c o u n t s , b u t th e y w e r e n o t s i g n i f i c a n t e i t h e r w hen

100
th e t h y r o i d u p t a k e w a s e x p r e s s e d i n t e r m s
th y ro id p e r

of c o u n ts p e r m i l l i g r a m

100 g r a m s b o d y w e i g h t o r w h e n e x p r e s s e d i n t e r m s o f

p e r c e n t u p ta k e .
The o v a rie c to m iz e d r a ts

w i t h t h e i r p i t u i t a r i e s i n t a c t sh o w e d

a s t a tis tic a lly sig n ific a n t i n c r e a s e

in

t h e u p ta k e of 1*^* by th e t h y ­

r o i d s of th e a n i m a l s i n j e c t e d w i th e i t h e r

6 r a t - u n i t s o r 300 r a t -

u n i t s of e s t r a d i o l b e n z o a t e w h e n c o m p a r e d to t h e i r c o n t r o l .
tio n s of e i t h e r

0.2 o r

0 .4 m i l l i g r a m s

d e c r e a s e d t h y r o i d u p ta k e of 1 ^ * .

o f p ro g e ste ro n e

The

w e r e fo u n d a l s o w h e n th e v a l u e s w e r e
m illig ra m

of t h y r o i d p e r

T he th y ro id g la n d s
ra ts

In je c ­

sig n ific a n tly

s a m e t r e n d s in 1*^* u p ta k e
e x p r e s s e d in c o u n ts p e r

s e c o n d o r p e r c e n t of i n j e c t e d d o s e .
of th e

o v a rie c to m iz e d -h y p o p h y se c to m iz ed

c o l l e c t e d 8 .0 4 p e r c e n t of t h e I

131

c o l l e c t e d by th e o v a r i e c ­

to m iz e d c o n tro ls .

Body w e ig h ts .

T h e b od y w e i g h t s o f the o v a r i e c t o m i z e d -

h y p o p h y se c to m iz ed a n im a ls w e re
t h e i r h y p o p h y s is i n t a c t .
to m iz e d r a t s

lig h te r

th a n th e a n i m a l s w ith

T h e b o d y w e i g h t s of th e h y p o p h y s e c ­

g iv e n 6 and 300 r a t - u n i t s

th e h y p o p h y s e c t o m i z e d r a t s

g iv e n

of e s t r a d i o l b e n z o a te and

0 .4 m illig r a m s of p ro g e s te ro n e

101

TABLE

X

T H E E F F E C T S O F E S T R O G E N AND P R O G E S T E R O N E ON I 131 U P ­
T A K E BY T H E TH Y R O ID G LA N D S O F H Y P O P H Y S E C T O M I Z E D O V A R 1 E C T O M IZ E D AND O V A R IE C T O M IZ E D R A T S
Body
W e ig h t

C ts ./s e c .

C ts ./m g .
w e t / l 00
sec.

1 O v a rie c to m iz e d -h y p o p h y s e c to m iz e d c o n tro l

1 37.75
± 2 .1 8

15.87
± 2 .8 7

1.28
± 0 .1 4

2 O v a rie cto m iz e d -h y p o p h y se c to m iz e d + 6 r a t- u n its
e s tr a d io l b e n zo ate

1 3 2 .7 5 '
± 2 .6 0

16.68
± 2.63

1.53
± 0 .2 4

3 O v arie cto m iz e d -h y p o p h y s e c t o m i z e d + 300 r a t u n its
e s tr a d io l b e n zo ate

1 3 0 .6 2 '
± 3 .9 7

13.82
± 1.60

1.23
± 0.12

4 O v a rie cto m iz e d -h y p o p h y s e c t o m i z e d + 0.2 m g .
p ro g e ste ro n e

1 3 8 .5 0
± 2 59

14.18
± 2.03

1.19
± 0.10

5 O v a rie cto m iz e d -h y p o p h y s e c t o m i z e d + 0 .4 m g .
p roge ste ro n e

1 3 0 .5 0 "
± 2 .8 9

1 0.1 4'
± 1.57

1.01
± 0 .10

b O v a rie c to m iz e d

173.75
± 3 .0 0

197.36
± 28.78

938
± 1.25

7 O v a rie c to m iz e d + 6 r a tu n its e s tr a d io l b e n z o a te

17 2.03
± 1.66

3 6 3 .2 3 "
± 28.55

1 6 .8 3 "
± 1.25

8 O v a r i e c t o m i z e d + 300 r a t u n its e s tr a d io l b e n z o ate

1 6 7 .67
± 2 .0 7

3 2 4 .7 1 "
± 2 2 .4 9

1 6 .3 1 "
± 0.94

9 O v a rie cto m iz e d
p ro g e ste ro n e

+ 0.2 m g .

170.11
± 2 .1 2

1 8 0 .3 4 '
± 1 8 .3 0

8 .9 9
± 0.89

10 O v a r i e c t o m i z e d
p ro g e ste ro n e

+ 0 .4 m g .

178.25
± 1.89

1 4 0 .0 4 "
± 1 5 .1 0

6 .1 0 "
± 0.17

c o n tro l

* S tan d ard e r r o r .
' S i g n if ic a n t a t 5 p e r c e n t l e v e l w h e n c o m p a r e d to i t s c o n t r o l .
M S i g n i f i c a n t a t 1 p e r c e n t l e v e l w h e n c o m p a r e d to i t s c o n t r o l .

102

TABLE

P et.
D ose

T h y r o id Wt.
in m g ./lO O
g m . / b o d y w t.

X

(C o n tin u e d )

T h y r o id
Wt. (dry)

P i t u i t a r y Wt.
in m g ./lO O
g m . body wt.

A d r e n a l Wt.
in m g ./lO O
gxn. body w t.

0 .8 0
± 0 .1 4

6 .2 9
± 0 .4 9

1.71
± 0 .2 7

—* -

1 6 .1 0
± 0 .5 0

0 .8 4
± 0 .1 4

6 .1 8
± 0 .8 7

1.42
± 0 .1 7

—»

1 5.9 7
± 0 .52

0 .7 0
± 0.25

6 .4 7
± 0 .2 6

1.25
± 0 .3 0

. . .

1 6 .0 6
± 0 .9 4

0.72
± 0 .1 0

6 .0 7
± 0 .3 9

1.31
± 0.17

ww

16.41
± 0.71

•

0.51
± 0.25

5 .8 8
± 0 .35

1 .16
=fc 0 .1 0

— —

1 7 .1 4
± 0 .4 4

9 .9 5
± 1.45

6 .7 8
± 0 .32

1.85
± 0 .6 6

5 .7 9
± 0 .1 4

2 6 .8 3
± 0 .9 4

1 8 .3 1 11
± 1 .4 4

6 .9 5
± 0 .3 6

2 .0 2
± 0 .1 4

6 .0 3
± 0.26

3 0 .4 8 '
± 0.73

1 6 .3 6 "
± 1 .1 4

7 .1 5
± 0.47

1.98
± 0 .1 4

6 .1 2
=fc 0 .1 7

3 1 .9 7 "
± 0.98

9 .0 9
± 0.29

6 .9 6
± 0.3 2

1.70
± 0 .1 4

5 .8 4
* 0 .2 0

3 1 .4 9 "
± 1.11

7 .0 6
± 0.76

7.18
± 0.25

1.65
± 0.17

5.81
± 0 .22

3 1 .1 8 "
± 0.41

I

103
w ere

s i g n i f i c a n t l y l i g h t e r t h a n t h a t of t h e i r

c o n tro l.

T h e re w ere

no s i g n i f i c a n t d i f f e r e n c e s b e t w e e n t h e b o d y w e i g h t s o f a n y of th e
g r o u p s w h ic h h a d t h e i r

h y p o p h y sis in ta c t.

T h y ro id w e ig h ts .

T h ere

w e r e no

sig n ific a n t d iffe re n c e s b e ­

tw e e n th e t h y r o i d w e i g h t s o f a l l g r o u p s w h e n e x p r e s s e d i n m i l l i ­
g ram s

per

100 g r a m s b o d y w e i g h t.

P itu ita ry

w e ig h ts.

T h ere

b e t w e e n th e p i t u i t a r y w e i g h t s
tre a te d

a n im a ls

and th e ir

A d ren al w e ig h ts.

t r e a t e d w ith e i t h e r

to t h e i r

of t h e

sig n ific a n t d iffe re n c e s

e stro g e n o r p ro g e ste ro n e

c o n tro ls.

T h ere

tw e e n t h e a d r e n a l w e i g h t s
ra ts

w e re no

w e r e no sig n ific a n t d if f e r e n c e s b e ­

of th e o v a r i e c t o m i z e d - h y p o p h y s e c t o m i z e d

e stro g e n o r

p ro g e ste ro n e

w h en c o m p a r e d

c o n tro l.
The o v a rie c to m iz e d

p ro g e ste ro n e

ra ts

t r e a t e d w ith e i t h e r

show ed a s ta tis tic a lly

a d r e n a l w e ig h ts

co m p ared

to t h e i r

e stro g e n o r

sig n ific a n t in c r e a s e
co n tro l.

in t h e i r

104
E x p e r i m e n t VIII
T h y r o tr o p h ic H o r m o n e P o t e n c y o f th e P i t u i t a r i e s and P l a s m a
of R a ts a t the S t a g e s o f th e E s t r o u s C y cle

A f te r finding th a t th e t h y r o i d s
an i n c r e a s e in the u p tak e of I * 31
o t h e r s t a g e s of the c y c le ,

of e s t r o u s r a t s

above

it s e e m e d

th e re w ere c o m p a rab le d i f f e r e n c e s

show ed

th a t c o lle c te d d u r in g

d e s i r a b l e to d e t e r m i n e w h e th e r

in the th y r o t r o p h ic p o te n c y of

t h e i r p i t u i t a r i e s and b lo o d s e r u m .
As th e d i f f e r e n c e s b e tw e e n .

th e

t h y r o tr o p h ic h o r m o n e c o n ­

te n ts of b o th p i t u i t a r y and b l o o d w e r e

e x p e c te d to be too s m a l l

to be d e t e c t e d b y the r e g u l a r

m e th o d s,

This method was

B esford

the uptake

of P

reported

32

by the

by

thyroids

cof

index of t hyrot r ophi c

h or mon e

that this met hod

sensitive

to

MateriaLs

and

was

a new te c h n iq u e w as u se d .
e_t aJL.

(1952).

two-day-old

potency.

chicks

The aut hor s

approximately

It employs
as

an

reported

0.02 Junkmann-

ochoel l er unit.

Four-day-old
pi t ui t a r i e s

of the

unsexed

rats

suspended in a saline

chicles

of each
solution.

stag e
T h e

Methods

we r e

used f or the a s s a y.

of the
sera

cycle

wer e

of the r a t s

The

pooled and
of each stage

105
of th e c y c l e w e r e
p itu ita ry

co n ta in e d in

je c te d p e r

c h ic k .

in je c te d p e r
p itu ita ry
of P

32

a l s o p o o le d .

in

c h ic k .

A d o s e of 2 m i l l i g r a m s of f r e s h

0.5 m i l l i l i t e r of a s a l i n e

O ne

and o n e -h a lf m i l l i l i t e r s

F o u r h o urs

su sp e n sio n o r
1 m illilite r

seru m

of e i t h e r th e

th e c h i c k s r e c e i v e d 20 m i c r o c u r i e s
s o lu tio n .

B o th i n j e c t i o n s w e r e

g iv e n i n t r a p e r i t o n e a l l y .

T w o h o u r s l a t e r th e

th e ir th y ro id s

o u t a n d w e ig h e d .

T he th y ro id s w e re

of p la s m a w e re

a f t e r th e i n j e c t i o n

of a s a l i n e

d isse c te d

s o lu t io n w a s i n ­

c h ic k s w e re

d r i e d by le a v in g t h e m

an o v e n a d j u s t e d to th e t e m p e r a t u r e

of 90*

k ill e d ,

f o r tw o h o u r s in

C e n tig ra d e .

They w ere

c o u n te d b y a G e i g e r C o u n t e r .

Re s u i t s

T h e a n a l y s i s of v a r i a n c e
n ific a n t d if f e r e n c e s b e tw e en
of a l l g r o u p s
The
sta tistic a lly

the body w e i g h t s o r t h y r o i d w e ig h ts

of c h i c k s .

c h ic k s

g iv e n 2 m i l l i g r a m s

c h ic k s

of r a t p i t u i t a r i e s

s i g n i f i c a n t i n c r e a s e in t h e i r

c o n te n t w h e n c o m p a r e d to th e
The

sh o w e d t h a t t h e r e w e r e no s i g ­

ra d io a c tiv e

fro m

p hosphorus

c o n tro ls.

phosp horus

g iv e n th e p i t u i t a r y

ra d io a ctiv e

sh o w e d a

c o n t e n t of the t h y r o i d s of the

e stro u s

ra ts

sh o w e d a s l i g h t b u t

I

106
TABLE

XI

C H IC K A S S A Y F O R T H Y R O T R O P H I C H O R M O N E P O T E N C Y O F
P IT U IT A R IE S O F F E M A L E R A T S A T TH E FO U R STA G ES
O F T H E E S T R O U S C Y C L E , U S IN G P 32

T re atm en t

Num ­
ber

Sex

B o d y W t.

T h y ro id
Wt. m g . /
100 g m .

C ts ./
S e c ./
T h y ro id

M a le s

6

5 1 .6 2
=fc 1.59*

9 .52
± 0.89

1.94
± 9 .2 9

F e m a le s

8

5 3.41
± 1.11

10.80
± 0.92

2 .38
± 0.22

M a le s

10

5 1 .8 8
± 0 .8 9

9 .3 4
± 0.82

3.42
± 0 .3 4

F e m a le s

17

5 1 .92
± 1.39

1 1.7 4
± 0.80

4 .1 0
± 0.41

M a le s

10

5 1 .53
± 1.64

±

11.33
0.80

3.75
± 0.41

F e m a le s

11

5 0.18
± 1.05

1 1.75
± 0.73

4.55
=b 0.42

M a le s

20

5 0 .23
± 1.09

10.66
± 0.62

3.97
± 0 .9 4

F e m a le s

10

5 1 .4 6
± 2.21

10.93
± 0 .8 4

4.08
± 0.33

M ales

13

5 3 .6 3
± 1.17

1 1 .1 4
± 0.73

3.65
± 0.31

F e m a le s

15

5 1.7 3
± 1.26

11.27
± 1.01

3.43
=fc 0 .3 4

C o n tro l

P ro e stru s

E stru s

M e te stru s

D ie stru s

* S ta n d a rd

erro r.

107
TABLE

X II

CH ICK ASSAY F O R T H Y R O T R O P H IC H O RM O N E P O T E N C Y
S E R U M O F F E M A L E R A T S A T T H E F O U R STA G ES
O F T H E ESTROUS C Y C L E

T re atm en t

Sex

Mu m •
ber

B o d y Wt.

T h y ro id
Wt. m g . /
100 g m .

C ts ./
S e c ./
T h y ro id

M a le s

6

5 1.6 2
± 1.59*

9 .5 2
± 0.89

F e m a le s

8

53.41
± 1.11

1 0.80
± 0.92

P ro e stru s

M ales
F e m a le s

0
8

5 0 .6 6
± 1.30

1 1.90
± 0 .37

2 .6 6
± 0.48

E stru s

M ales
F e m a le s

2
4

4 8.98
± 1.82

10.33
± 1.05

3.05
dfc 0.39

M e te stru s

M a le s
F e m a le s

2

4

4 8 .08
± 1.62

11.59
± 0.46

2.41
± 0.1 0

D ie stru s

M a le s
F e m a le s

3
3

53.08
db 1.47

9 .77
± 0.77

2.38
± 0.08

C o n tro l

0

♦ S ta n d ard e r r o r .

2 .1 9
± 0.16

108
n o n s i g n i f i c a n t i n c r e a s e w h e n c o m p a r e d to t h a t o f th e t h y r o i d s of
c h i c k s i n j e c t e d w ith p i t u i t a r i e s of t h e r a t s
th re e

sta g e s

of th e e s t r o u s

k ille d a t th e o th e r

c y c le .

W hen i n je c te d w ith r a t

s e r u m , th e o n ly g r o u p o f c h i c k s

w h ic h s h o w e d a

sig n ific a n t in c r e a s e

c o n te n t of t h e i r

t h y r o i d s w h e n c o m p a r e d to th e m a l e

th e a v e r a g e

of b o th m a l e s

j e c t e d w ith s e r u m

fro m

d i f f e r e n c e s b e t w e e n th e
th y ro id s

of c h i c k s

in th e

and fe m a le s

e stru s

ra ts.

ra d io a c tiv e p h o sp h o ru s

to g e th e r, w e re th o se in ­
T h e r e w e r e no s ig n ific a n t

ra d io a c tiv e p h o sp h o ru s

tre a te d

w ith s e r u m

c o n tro ls o r

of r a t s

c o n t e n t o f th e
a t th e fo u r

sta g e s

of th e c y c l e .
O n e c o u ld c o n c l u d e , th o u g h n o t d e f i n i t e l y ,
tro p h ic

p o t e n c y of th e p i t u i t a r i e s

of e s t r u s

t h a t th e t h y r o ­

r a t s have a slig h tly

h i g h e r p o t e n c y w h e n c o m p a r e d to t h o s e of r a t s a t th e o t h e r t h r e e s t a g e s
of t h e e s t r o u s

cy c le .

F ro m

th e t h y r o t r o p h i c h o r m o n e
ceeds

th a t of r a t s

th is

e x p e rim e n t a lso , it

c o n t e n t of th e

a t th e o th e r t h r e e

A s th is m e th o d of a s s a y in g
it s e e m s p ro b a b le
one

seru m

seem s

of e s t r u s

th a t

ra ts

ex­

s t a g e s of th e c y c l e .

th y r o tr o p h ic h o rm o n e i s new ,

t h a t w ith f u r t h e r i m p r o v e m e n t o f th e t e c h n i q u e s

c o u ld o b t a i n m o r e

c o n c lu siv e

re su lts.

By u sin g

la rg e r doses

109
of r a d i o a c t i v e p h o s p h o r u s , p i t u i t a r y a n d s e r u m
d iffe re n c e s b e tw e en g ro u p s

s h o u ld be fo un d .

l a r g e r a b so lu te

DISCUSSION

The d a ta p r e s e n t e d in e x p e r i m e n t I s h o w e d an i n c r e a s e d
o x y g e n c o n s u m p t io n o f r a t s during e s t r u s .
w a s an i n c r e a s e
d ie str u s.

O n the a v e r a g e t h e r e

o f 16.65 p e r c e n t du ring e s t r u s o v e r that during

T h is i s in a g r e e m e n t w ith the fin d in g s of L a q u e u r e t

a l . (1 9 2 6 ), who found th a t the b a s a l m e t a b o l i s m

rose

20 p e r c e n t

in n o r m a l and o v a r i e c t o m i z e d r a t s w ith in th r e e day s during the
in je c tio n o f e s t r o g e n .
S lo n a k e r e t a l. (1927) and Wang (1932)
rat the e s t r u s p h a s e i s

a c c o m p a n ie d w ith a p r o n o u n c e d i n c r e a s e

in l o c o m o t o r a c t i v i t y and an i n c r e a s e
B r o b e c k e t al.
10 to

n o t ic e d that in the

in e n e r g y e x p e n d itu r e .

(1947) a l s o found that e s t r o u s

12 g r a m s in the individ ual c y c l e

r a ts l o s t f r o m

due to d e c r e a s e d fo o d in ­

take and i n c r e a s e d e x p e n d itu r e of e n e r g y .

T h ey thought that the

p e r io d ic c h a n g e s in the r a t e s of e n e r g y in tak e and e x p e n d itu r e
a p p e a r e d to be d e r iv e d f r o m e it h e r h y p o p h y sia l o r o v a r ia n c y c l e s
w hich th e y s t a t e d i s c o m p a t ib le w ith the h y p o t h e s is that p r o c e s s e s
of e n e r g y e x c h a n g e

are

r e g u la t e d and in t e g r a t e d by s p e c i a l i z e d

c e l l s , p o s s i b l y by c e l l s w h ic h l i e w ithin the h yp o th a la m u s.

We

a ls o b e lie v e

t h a t t h e v a r i a t i o n in e n e r g y e x c h a n g e

in c r e a s e d oxygen c o n su m p tio n d u rin g e s t r u s

as in d ic a te d by

is m o s t p ro b a b ly c o n ­

t r o l l e d b y h y p o p h y s i a l o v a r i a n a n d t h y r o i d h o r m o n e s , e v e n th o u g h
th e re w as no lo s s

i n b o d y w e ig h t.

E s tr o g e n p re d o m in a tin g d u rin g e s t r u s
m e ta b o lic e ffe c ts ,

in c re a s in g

m ig h t have d ir e c t

oxygen c o n su m p tio n o r p o s s ib ly a c t ­

ing i n d i r e c t l y v i a th e p i t u i t a r y , t h y r o i d a n d a d r e n a l g l a n d s .
U n d e r o u r c o n d i t i o n of s t u d y i n g th e

ra ts

under b asal con­

d i t i o n s t h e r e w e r e n o s i g n i f i c a n t d i f f e r e n c e s b e t w e e n th e b o d y w e ig h t
of th e a n i m a l s a t th e d i f f e r e n t s t a g e s o f th e e s t r o u s c y c l e .
W hen th e

r a t s w e re fed ad lib itu m

fo u n d t h a t e s t r o u s
cy c le .
le ss
day.

ra ts

lo s t from

10 to

12 g r a m s

T h e y a l s o f o u n d t h a t fo o d i n t a k e

th a n th e i n t a k e d u r i n g

B r o b e c k e t a l . (1947)
in th e in d iv i d u a l

d u rin g e s t r u s

d i e s t r u s , by as

w as alw ay s

m uch as 6 g r a m s p e r

T h i s , t o g e t h e r w i th th e i n c r e a s e d e n e r g y e x p e n d i t u r e d u r i n g

e s tr u s . m ig h t p a r tly
ra ts.

T horn e t a l.

d ie ta ry

e x p l a i n th e d e c r e a s e

(193 8) r e p o r t e d t h a t n o r m a l w o m e n in w h o m

re s tric tio n s w ere

i m p o s e d w e r e o b s e r v e d to g a i n w e ig h t

d u r i n g th e i n t e r m e n s t r u a l a s w e l l a s
p h a s e of th e c y c l e .
strik in g

in b o d y w e i g h t s of s u c h

An i n c r e a s e

d u r i n g th e p r e m e n s t r u a l

in a p p e p it e

and t h i r s t w as a

s y m p t o m n o t e d d u r i n g th e p r e m e n s t r u a l p e r i o d .

T hey

112
c o n c lu d e d t h a t th e i n c r e a s e
e stro g e n

and p ro g e s te ro n e

in t h e

s e c r e t i o n of s e x h o r m o n e s b o th

(w h ic h in d u c e

r e t e n t i o n of s o d iu m ,

c h l o r i d e a n d w a t e r d u r i n g th e i n t e r m e n s t r u a l a s w e ll a s th e p r e ­
m e n stru a l p h ase

of th e c y c le )

t o g e t h e r w ith th e i n c r e a s e

t it e a n d t h i r s t a p p e a r to b e c o n t r i b u t i n g f a c t o r s
g a in , t h a t o c c u r s

d u r i n g th e m e n s t r u a l c y c l e .

in a p p e ­

in b o d y w e ig h t
T h e y a l s o found

t h a t th e o n s e t of m e n s t r u a t i o n w a s a s s o c i a t e d w ith an i n c r e a s e of
r e n a l e x c r e t i o n of s o d i u m , c h l o r i d e

and w a te r.

O u r d a t a d id n o t s h o w a d i s t i n c t v a r i a t i o n in th e b a s a l
te m p e ra tu re s
(1947)

of r a t s

d u r i n g th e e s t r o u s

c y c le .

r e p o r t e d t h a t lo w b o d y t e m p e r a t u r e s w e r e

n o t i c e d in r a t s

w ere

b efore o r a f te r e s tr u s .
d u r in g d i e s t r u s .
te m p e ra tu re s.
tr a te d fe m ale

c o n siste n tly

on th e a f t e r n o o n j u s t p r e c e d i n g th e n ig h t of e s t r u s .

The t e m p e r a t u r e s

a l s o o c c a s i o n a l l y found to be low a d ay
It w as

d e f i n i t e l y l o w e r d u r in g e s t r u s

It s h o u ld b e n o t i c e d t h a t t h e s e
N i e b u r g a n d G r e e n b l a t t (1948)

a b o v e t h a t of th e c a s t r a t e d

p r o d u c e s a d e c r e a s e of b o d y t e m p e r a t u r e .

s h o w e d t h a t in c a s ­
in c re a se s

c o n t r o l s w h ile e s t r o g e n
R o th c h ild a n d R a p p o r t

r e p o r t e d a l s o t h a t the a d m i n i s t r a t i o n of p r o g e s t e r o n e

m ale c r e t i n s

o r fe e b le -m in d e d hum ans

th a n

w ere not b a sa l

r a t s , th e a d m i n i s t r a t i o n of p r o g e s t e r o n e

the t e m p e r a t u r e

(1952)

B r o b e c k e t a l.

to

c a u s e d a n e l e v a t i o n of

113
b od y t e m p e r a t u r e , a n d t h a t s u c h a n e f f e c t w a s n o t m e d i a t e d t h r o u g h
the t h y r o i d g la n d .
W h ite la w (1952) on th e o t h e r h a n d c o n c lu d e d t h a t e n d o g e n o u s
p ro g e ste ro n e

is n o t th e h o r m o n e

m a i n t e n a n c e of t h e t h e r m o g e n i c
s tr u a l c y c le .
th e d o s a g e

ra te

a n d p e r i o d of a d m i n i s t r a t i o n ,

The
th e re

ra d io a c tiv e
t h a t th e

re su lts

re su lts.

fro m

th e se fa c to rs

G r i f f i t h e_t a^. (1929) fo u n d t h a t

e x p e rim e n ts

io d in e b y th e

r a ts , w as

II a n d 111 s h o w e d t h a t in

sig n ific a n t in c r e a s e

th y ro id s

u p ta k e of m e t e s t r o u s

d ie stru s

in th e u p ta k e of

d u rin g e s t r u s .

ra ts,

I t w a s a l s o fo u n d

th o u g h s i g n i f i c a n t l y l e s s

th an

s i g n i f i c a n t l y h i g h e r th a n t h a t o f r a t s

in

and p r o e s tr u s .

In e x p e r i m e n t II th e
9 4 7

sin c e

and m e ta b o lism .

is a s ta t i s t i c a l l y

t h a t of e s t r o u s

(1

d u r i n g th e m e n ­

i s n o s i g n i f i c a n t c o r r e l a t i o n b e t w e e n th e i n t r a i n d i v i d u a l v a r i ­

a t i o n s of t e m p e r a t u r e

ra ts

e ffe c ts o c c u rrin g

or

A s w e w i ll p o i n t o u t l a t e r o n e s h o u l d k e e p in m i n d

c a n c o n s i d e r a b l y v a r y th e
th e re

r e s p o n s i b l e f o r e i t h e r th e r i s e

) re p o rte d ,

r a t s w e re fe d a r e g u l a r d ie t.

a s m e n tio n e d b e fo re , th a t e s tr o u s

l e s s fo o d d a i l y th a n d i e s t r o u s
ta k e w o u ld a l s o b e l e s s

ra ts.

d u rin g th is

ra ts

B robeck

eat 6 g ram s

C o n s e q u e n t ly , th e io d in e i n ­
sta g e .

114
A n o t h e r f a c t i s t h a t t h e u p ta k e of I
tio n a l to th e io d id e i n t a k e a s
(1950).

131

is i n v e r s e l y p r o p o r ­

r e p o r te d b y V a n d e rlea n and G r e e r

T h e y a l s o a d d e d t h a t th e io d in e c o n c e n t r a t i n g m e c h a n i s m

a p p e a r s to b e

po

r e g u l a t e d t h a t u n d e r c o n d it io n s of v a r y i n g io d in e

s u p p ly th e e f f i c i e n c y o f io d in e a c c u m u l a t i o n c a n b e g r e a t l y a l t e r e d ;
f o r e x a m p l e w h e n io d in e

is d e f i c i e n t , t h e r e i s a c o m p e n s a t o r y a l ­

t e r a t i o n of t h y r o i d f u n c t i o n s o t h a t th e a v a i l a b l e
can be tra p p e d f o r m o re
T h e s e tw o f a c t o r s

s u p p ly of io d in e

efficien c y .
s u g g e s t e d th e p o s s i b i l i t y t h a t th e v a r i a ­

tio n s in t h y r o i d u p ta k e o b s e r v e d in o u r f i r s t e x p e r i m e n t m i g h t
s im p ly b e d ue to th e v a r i a t i o n in fo o d in ta k e a n d th e c o n s e q u e n t
v a r i a t i o n in N a l u p ta k e .

I t w a s th e n d e c i d e d to s t a n d a r d i z e th e

u p ta k e of N a l.
In e x p e r i m e n t III th e

r a t s w e r e f e d a n io d in e d e f i c i e n t d i e t

a n d d r a n k d o u b le d i s t i l l e d w a t e r .

They w ere

in je c te d in tra p e rito -

n e a l l y d a i ly f o r f i f t e e n d a y s w ith 5 m i c r o g r a m s of N a l.
t h e s e c o n d it io n s we o b s e r v e d a n e x a c t l y

U nder

s i m i l a r p a t t e r n of t h y r o i d

u p ta k e to t h a t fo un d in th e p r e c e d i n g e x p e r i m e n t w h e r e th e a n i m a l s
w e r e f e d a r e g u l a r d i e t a n d d r a n k ta p w a t e r .
T he

re su lts fro m

th a t such c y c lic

t h e s e tw o e x p e r i m e n t s p o in t e d o u t c l e a r l y

v a r i a t i o n in t h y r o i d a c t i v i t y i s n o t due s im p l y to

115
v a r i a b i l i t y in th e a m o u n t of i n g e s t e d io d in e , b u t i t is d e f i n i t e l y a
horm onal m e c h a n is m

w h ic h is

c l o s e l y r e l a t e d to o v a r i a n a c t i v i t y .

A n o t h e r p o i n t w e w o u ld l i k e to d e f e n d b e f o r e we go a n y
fu rth e r is:
th y r o i d b e

h o w r e l i a b l y c a n th e
used as

r a d i o a c t i v e io d in e u p ta k e b y th e

a n i n d e x of t h y r o i d a c t i v i t y ?

T here

i n v e s t i g a t o r s w h o lo o k w i t h s u s p i c i o n u p on d a t a w h e r e
is u s e d a s
tim e
e t a l.

to

a n i n d e x of t h y r o i d a c t i v i t y .

rep o rt h ere

(1951).

of i o d i n e

In t h e i r

w a s d e t e r m i n e d b y the

I t is n e c e s s a r y a t t h i s

of th e i n v e s t i g a t i o n s of D o u g h e r ty

a n d th e

c o n c lu d e d f r o m

th e ir e x p e rim e n ts

r e l e a s e of i o d i n e - c o n t a i n i n g h o r ­

e x p e rim e n ts

H o w ever,

th e

ra te

of u p ta k e of io d in e

a m o u n t of r a d i o i o d i n e fo u n d in th e g la n d

a f t e r th e i n j e c t i o n .

ing th e g l a n d m i n u s
p erio d .

1*^* u p ta k e

s im u lta n e o u s ly , c o n tin u o u sly and a t an a p p ro x im a te ly

co n sta n t ra te .

fo u r h o u rs

re su lts

T h ese in v e stig a to rs

t h a t th e u p ta k e
mone o c c u r

th e

a re m any

T h is

r e p r e s e n t e d th e a m o u n t e n t e r ­

t h a t l e a v i n g th e t h y r o i d o v e r th e f o u r - h o u r

th ey

s a y t h a t th e a m o u n t of r a d i o a c t i v e P B I

in th e b l o o d w a s o n ly a b o u t 2 p e r c e n t of th e a m o u n t of I
tw o t h y r o i d l o b e s .
ic a lly bound f r o m
it p o ssib le

T h erefo re,

th e

re le a se

131

in th e

of th e a m o u n t o r g a n ­

th e t h y r o i d m u s t h a v e b e e n s m a l l e n o u g h to m a k e

to c o n s i d e r th e t h y r o i d c o u n ts a s a g o o d in d e x o f th e

a m o u n t of r a d i o i o d i n e

e n t e r i n g the g la n d s i n c e th e t i m e

of i n j e c t i o n .

116
E x a m i n a t i o n of i n d i v i d u a l d a t a i n d i c a t e d t h a t th e P B I a c t i v i t y w a s
h ig h w h e n th e t h y r o i d

ra ts.

r a d i o a c t i v i t y w a s h ig h a n d v ic e v e r s a .

In th e m o u s e

th e c a s e w a s

Though th e r e

w as

of two s p e c i e s
It is tr u e
e stro u s

c y c l e , th e h i g h e s t u p ta k e of r a d i o a c t i v e

a t t a i n e d b y th e m i c e

d a t a of e x p e r i m e n t s

H ere

is

rat

w ith d i f f e r e n t p a t t e r n s

sh ow n b y th e

of t h y r o i d a c t i v i t y .

v a r i a t i o n th r o u g h the

s h o w e d m a x i m a l a c t i v i t y d u r in g e s t r u s ,

t h y r o i d h a d i t s h i g h e s t a c t i v i t y d u r in g p r o e s t r u s .

I t is g e n e r a l l y a g r e e d t h a t th e m o u s e
t h y r o i d a n i m a l a n d t h a t th e
as

as

a good i l l u s t r a t i o n

s p e c ie s e x h ib ite d a c y c lic

c y c l e b u t th e

w h ile th e m o u s e

in p r o e s t r u s ,

IV (A) a n d (B).

of a n i m a l s

th a t b o th

t h a t o b s e r v e d in

a c y c l i c v a r i a t i o n in t h y r o i d a c t i v i t y w hen

c o r r e l a t e d to th e e s t r o u s
io d in e w a s

d iffe ren t fro m

i n d i c a t e d in th e w o r k

is a r e l a t i v e l y h y p o ­

r a t is a s l i g h t l y h y p e r t h y r o i d a n i m a l

r e p o r t e d b y M a q s o o d and R e in e k e

(1950),

N o v a k (1 9 50 ), M e i t e s a n d C h a n d r a s h a k e r (1949), a n d J o h n s o n a n d
M e ite s

(1951).
In the

m ouse

it s e e m s

t h a t e s t r o g e n a t a v e r y lo w l e v e l

h a s a t a r g e t e f f e c t on th e t h y r o i d g iv in g a s p u r t of i n c r e a s e d
a c t i v i t y f o llo w e d b y a d e p r e s s i o n .
th e m o u s e

responds

p o s s ib ly a tim e

to e s t r o g e n

f a c t o r is

P erh ap s

th e t h y r o i d g la n d of

a t a lo w t h r e s h o l d th e n d e c l i n e s ,

in v o lv e d a l s o , a f t e r w h ic h th e t h y r o i d

117
g la n d b e c o m e s

r e f r a c t o r y to e s t r o g e n , o r p o s s i b l y it b e c o m e s

f r a c t o r y to h ig h l e v e l s
t h a t th e t h y r o t r o p h i c

of e s t r o g e n .

horm one

re­

A n o th e r ex p la n a tio n m a y be

d e p o t is e x h a u s t e d q u ic k ly .

So f a r w e p o i n t e d o u t t h a t o x y g e n c o n s u m p t i o n of th e f e m a l e
r a t is i n c r e a s e d d u rin g e s t r u s .
u p ta k e of r a d i o a c t i v e io d i n e
It th e n g r a d u a l l y f a l l s ,
le v e l d u rin g d i e s t r u s
The o r g a n s
a c tiv ity a r e

We a l s o fo u n d t h a t in t h e

r a t th e

r e a c h e s i t s h i g h e s t p e a k d u r in g e s t r u s .

sta rtin g

a t m e te s tr u s , and a tta in s

its lo w e st

and p r o e s tr u s .

i n v o lv e d in

such a cy c lic

v a r i a t i o n of t h y r o i d

m o s t p r o b a b l y th e o v a r i e s , a d r e n a l s

and p itu ita ry .

T he r e l a t i o n s h i p b e t w e e n th e t h y r o i d a n d t h e s e g l a n d s h a s b e e n
s t u d i e d in e x p e r i m e n t s
A sin g le
d io l b e n z o a t e ,
o v a rie c to m iz e d

V, VI, a n d VII.

in je c tio n of s ix

a dose la rg e
ra ts

c e e d e d in i n c r e a s i n g

ra t-u n its

(1 m i c r o g r a m )

e n o u g h to e l i c i t a n e s t r u s

w it h i n f o r t y - e i g h t h o u r s

sm ear

a f te r in je c tio n ,

s i g n i f i c a n t l y the u p ta k e of r a d i o a c t i v e

S t u d ie s of th e e f f e c t of e s t r o g e n on th e t u r n o v e r
I 131 b y th e t h y r o i d s
and m ic e ,

of e s t r a ­

of c h i c k s ,

i n c r e a s e d th e o u tp u t of I

suc­
io d in e .

r a te of

E p s t e i n a n d W o l t e r i n k (1949), r a t s

W o l t e r i n k e t a l . (1 95 0 ), a n d W o l t e r i n k

th a t s m a ll d o s e s of e s t r o g e n

in

(1 m i c r o g r a m )

(1952)

sh o w e d

d a ily f o r th re e

b y the t h y r o i d , w h ile l a r g e

days

d o s e s of

118
10 o r

100 m i c r o g r a m s

of e s t r o g e n g i v e n d a i l y f o r t h r e e
131

a lso a m a s s iv e

sin g le

In o t h e r w o r d s ,

a d o s e of e s t r o g e n l a r g e e n o u g h to b r i n g a r a t

in to e s t r u s

d o s e of e s t r o g e n d e p r e s s e d I

days and
tu rn o v e r.

i s a b l e t o i n c r e a s e th e i o d in e c o n c e n t r a t i n g c a p a c i t y

of i t s t h y r o i d .

It a lso in c re a s e s

th e r a t e

of r e l e a s e

of t h y r o i d

horm o n e.
T h e s e tw o e f f e c t s
tro p h ic h o rm o n e .
to p r o v e

The

are

c h a ra c te ristic

re su lts fro m

th is n ew p o in t.

of t h e e f f e c t of t h y r o -

e x p e r i m e n t s VII a n d VIII h e lp

In h y p o p h y s e c t o m i z e d a n i m a l s th e

sam e

d o s e of e s t r o g e n f a i l e d to e x e r c i s e th e u s u a l s t i m u l a t i n g e f f e c t
o n the t h y r o i d .
th y ro id a s

I t w a s u n a b le to i n c r e a s e

of th e

one, th a t th e r e
seru m

is

of e s t r u s

ra ts

gave

u p ta k e b y th e

re le a se d fro m

h o r m o n e p o t e n c y o f th e p i t u i t a r y

a n i n d i c a t i o n , th o u g h n o t a s i g n i f i c a n t

a h ig h e r th y ro tro p h ic

h o r m o n e c o n t e n t in th e

ra ts.

S a x to n a n d G r e e n
th e f e m a l e

(1942) fo u n d t h a t t h y r o t r o p h i c h o r m o n e i s
r a b b it h y p o p h y sis a f t e r c o itu s to g e th e r

w ith F S H a n d L H a n d p r o b a b l y A C T H .
o ccu rs

131

i t d id in th e a n i m a l s w ith th e h y p o p h y s i s i n t a c t .

T h e a s s a y of t h y r o t r o p h i c
and s e r u m

th e I

o n ly a f t e r c o i t u s , w h ile in th e

O v u l a t i o n in th e
r a t it is

ra b b it

sp o n tan eo u s.

In

119
o th e r w o rd s,

th e re

is

a t o v u la ti o n in b o t h

a n i n c r e a s e d s e c r e t i o n of TSH p r i o r to a n d

sp e c ie s.

The p r e s e n c e

of th y ro tro p h ic h o rm o n e

t h y r o i d g l a n d to c o n c e n t r a t e

i s n e c e s s a r y f o r th e

th e io d id e c i r c u l a t i n g In th e b lo o d .

F o llo w in g h y p o p h y s e c t o m y t h i s c a p a c i t y i s l o s t a lth o u g h n o t e n ­
tire ly .

R a n d a l l a n d A l b e r t (1951) fo u n d t h a t fo llo w in g h y p o p h y s e c ­

to m y th e

r a t th y ro id

c o l l e c t e d a b o u t 12 p e r c e n t a s m u c h io d in e a s

b e fo re h y p o p h y se c to m y .

T h ey a l s o fo u n d t h a t th e d e f e c t in c o l l e c ­

tio n of io d in e o c c u r s

s o o n a f t e r th e o p e r a t i o n a n d b e c o m e s m a x i m a l

b e tw e e n f iv e a n d s i x

days

a f t e r th e o p e r a t i o n .

F iv e o r six d ay s

a f t e r h y p o p h y s e c t o m y t h e t h y r o i d a l u p ta k e of I
i m a l v a lu e o f a b o u t
th r o u g h o u t th e
fro m

8 p e r c e n t of n o r m a l a n d r e m a i n e d a t t h i s l e v e l

s u b s e q u e n t p e r i o d of o b s e r v a t i o n s .

The d a t a o b t a i n e d

e x p e r i m e n t V II s h o w e d t h a t the o v a r i e c t o m i z e d - h y p o p h y s e c <

to m iz e d

ra ts

of th e I
are

reached a m in ­

1 31

th irte e n

d a y s a f t e r th e o p e r a t i o n c o l l e c t e d

c o l l e c t e d b y th e o v a r i e c t o m i z e d c o n t r o l s .

s i m i l a r to t h o s e

8.04 p e r c e n t

T hese v a lu e s

o b t a i n e d b y R a n d a ll a n d A l b e r t .

P r o l o n g e d a d m i n i s t r a t i o n of a l a r g e d o s e of e s t r a d i o l b e n ­
z o a te a t th e d o s a g e

ra te

of 300 r a t - u n i t s

(50 m i c r o g r a m s )

10 t i m e s

in a p e r i o d of t w e n t y d a y s h a d no e f f e c t on th e t h y r o i d u p ta k e of
ra d io a ctiv e

io d in e .

120
O u r d a ta in th is c a s e a g r e e w ith th o se o f P a s c h k i s e t a l .
(1 9 4 8 ), w h o r e p o r t e d t h a t 50 m i c r o g r a m s o f e s t r a d i o l b e n z o a t e f o r
t w e l v e , e l e v e n , a n d t h i r t e e n d a y s d id n o t h a v e a n y e f f e c t o n I
u p ta k e w h e n c o m p a r e d t o th e c a s t r a t e d c o n t r o l .
(1 9 5 0 ,

1951) r e p o r t e d s i m i l a r r e s u l t s

H ow ev er,

131

M oney e t al.

w ith e s t r a d i o l b e n s o a t e .

5 m i c r o g r a m s of e s t r o n e g iv e n d a ily f o r te n d ay s c a u s e d

a sig n ific a n t r i s e

i n 1*^* u p ta k e w i t h n o i n c r e a s e in t h y r o i d

w e ig h t.
W h ile p r o l o n g e d a d m i n i s t r a t i o n of a l a r g e
b e n z o a te f a ile d to

sh o w a d e t e c t a b l e

a s i n g l e i n j e c t i o n of 300 r a t - u n i t s
b en zo ate

re su lte d

d iffe re n t fro m
of six

th e

ra t-u n its.

dose

of e s t r a d i o l

c h a n g e in t h y r o i d a c t i v i t y ,

(50 m i c r o g r a m s )

in a n i n c r e a s e d u p t a k e of 1

131

of e s t r a d i o l

n o t sig n ific a n tly

i n c r e a s e d u p ta k e i n d u c e d b y a s i n g l e i n j e c t i o n
T h is

show s c l e a r l y

th a t it

w a s n o t th e d o s e b u t

th e p e r i o d of a d m i n i s t r a t i o n w h ic h r e s u l t e d in o u r f a i l u r e to d e t e c t
a n y d i f f e r e n c e s b e t w e e n th e
p e r i o d a n d th e c o n t r o l s .

ra ts

t r e a t e d w ith e s t r o g e n f o r a lo n g

T he m o s t p r o b a b l e e x p l a n a t i o n f o r s u c h

a p h e n o m e n o n i s t h a t th e f i r s t fe w i n j e c t i o n s of e s t r o g e n w i l l s t i m ­
u l a t e th e t h y r o i d v i a th e p i t u i t a r y g l a n d w h ic h s e c r e t e s t h y r o t r o p h i c
ho rm o n e.

W ith p r o l o n g e d a d m i n i s t r a t i o n of e s t r o g e n

the

121
th y ro tro p h ic

h o rm o n e d e p o ts a r e

e x h a u s t e d a n d c o n s e q u e n t l y th e

t h y r o i d g l a n d w i l l b e u n a b l e to c o n c e n t r a t e
P in c u s and W e rth e ss in
c a t i o n of a d o s a g e
c re a sin g

t h y r o i d w e ig h t , a n d t h a t i t i s o n ly a m a t t e r of the p e r i o d

a f t e r fiv e

They got a m a x im u m

d ay s of in je c tin g e s t r i n ,

u a l ly to a m i n i m u m

in je c tio n .

th e

a fte r fo rty

e f f e c t of e s t r i n

tra tio n

show ed th a t th e r e w as no in d i­

r e l a t i o n to th e e f f e c t of e s t r i n i n j e c t i o n s on i n ­

of a d m i n i s t r a t i o n .

th e

(1933)

io d in e a s b e f o r e .

in t h y r o i d w e i g h t

and th is d e c r e a s e d f a i r l y g r a d ­

d a y s of i n j e c t i o n , in d i c a t i n g t h a t

on th e t h y r o i d is n o t s u s t a i n e d w ith p r o l o n g e d

K o e n ig e t a l .

of e s t r o n e

in c re ase

(1945)

a l s o fo u n d t h a t p r o l o n g e d a d m i n i s ­

r e s u l t e d in a d e c r e a s e

in th e io d in e c o n t e n t of

th y ro id s.
P ro g e ste ro n e

m illig ra m

g iv e n a t th e d o s e l e v e l s of 0 .2 a n d 0.4

s u c c e e d e d in d e c r e a s i n g th e

six -h o u r I

131

u p ta k e b y th e

t h y r o i d s of o v a r i e c t o m i z e d r a t s f o r t y - e i g h t h o u r s a f t e r p r o g e s t e r o n e
ad m in istra tio n ,

as

s h o w n in e x p e r i m e n t s

V a n d VII.

d e m o n s t r a t e d t h a t a d o s e of 0 .4 m i l l i g r a m

of p r o g e s t e r o n e

a b l e to c o u n t e r a c t th e e f f e c t of s i x r a t - u n i t s
w ith a r e s u l t a n t d e c r e a s e
The dose
1

th e

I

O

in I

131

of 0 .8 m i l l i g r a m

It w a s a l s o
w as

of e s t r o d i o l b e n z o a t e

u p ta k e .
p ro g e ste ro n e

a lo n e i n c r e a s e d

1

u p ta k e , w h ile th e

s a m e d o s e of p r o g e s t e r o n e

a n t a g o n iz e d

122
th e s t i m u l a t i n g e f f e c t of e s t r o g e n o n th e t h y r o i d .
T he o n ly p r i o r in v e s tig a tio n s w h e re I
th e

s tu d y o f t h e e f f e c t o f p r o g e s t e r o n e

t h o s e o f M o n e y e t a l . (1 9 50 ,

1951).

d o s e of 50 m i l l i g r a m s p r o g e s t e r o n e

131

has been used fo r

on t h y r o i d a c t i v i t y w e r e

They re p o rte d th a t a to ta l
i n j e c t e d in to m a l e

r a t s in a

p e r i o d of t e n d a y s i n c r e a s e d th e u p ta k e of 1*^* b y th e t h y r o i d
w ith o u t i n f l u e n c i n g th e t h y r o i d w e i g h t s .
H isto lo g ic a l

s t u d i e s of h y p e r p l a s t i c t h y r o i d s of r a t s h a v e

sho w n t h a t th e p a r e n t e r a l a d m i n i s t r a t i o n o f p r o g e s t e r o n e
p r o g e s te ro n e p lu s
p o rte d by E m ge
(1941).

e stro g e n w ere

a lo n e o r

a b le to i n h i b i t h y p e r p l a s i a a s

re­

a n d L a q u e u r (1941) a n d S c h i ll in g a n d L a q u e u r

They a lso

r e p o r t e d t h a t a lt h o u g h e s t r o g e n f a i l e d to c h a n g e

th e t h y r o i d w e i g h t s

of t h y r o h y p e r p l a s t i c

tro n e and p ro g e s te r o n e

ra ts , p ro g e ste ro n e o r e s ­

t o g e t h e r d e c r e a s e d th e t h y r o i d w e i g h t s .

The p o s s ib ility th a t p r o g e s te r o n e

m ig h t e x e r t its

a c t i o n on th e t h y r o i d m a i n l y v i a th e p i t u i t a r y w a s
w a s fo u n d t h a t a d o s e

of 0 .4 m i l l i g r a m

to o v a r i e c t o m i z e d - h y p o p h y s e c t o m i z e d
sig n ific a n t d e c r e a s e

in th e u p ta k e of I

r u l e d o u t.

p ro g e ste ro n e

ra ts

in h ib ito ry
It

a d m in iste re d

cau sed a sta tistic a lly
w h e n c o m p a r e d to t h a t

of c o n t r o l o v a r i e c t o m i z e d - h y p o p h y s e c t o m i z e d

ra ts.

123
C u tu ly (1941) fo u n d t h a t th e a d m i n i s t r a t i o n of 0 .5 to 3.0
m illig ra m s

d a ily of p r o g e s te r o n e

to c a s t r a t e d a d u l t m a le

and fe m a le

r a t s d id n o t c o r r e c t h i s t o l o g i c a l c a s t r a t i o n c h a n g e s of th e a n t e r i o r
p itu ita ry .

The

w e i g h t c h a n g e s of p i t u i t a r i e s of f e m a l e s w e r e
a lso re p o rte d th a t p ro g e ste ro n e

ir­

re g u la r.

They

did n o t h a v e a

s e le c tiv e

i n h i b i t o r y a c t i o n on th e d i f f e r e n t c o m p o n e n ts of g o n a d o ­

tro p h in s.
By a p p ro p ria te h orm one
p o ssib le

to i m i t a t e

o c c u rrin g

in s p a y e d r a t s

it w a s

c l o s e l y th e c h a n g e s in t h y r o i d io d in e u p ta k e

d u rin g a n o rm a l e s tr o u s

of th e fo llo w in g p a g e ,
lu stra te

in je c tio n s

c y c le .

c o lle c ted fro m

The d a ta a t th e top

T a b l e s II, IV, a n d IX, i l ­

th a t th is w as a c co m p lish ed .
A sta g e

ra t-u n its
creased

s i m i l a r to e s t r u s

of e s t r a d i o l b e n z o a t e .
u p ta k e

s e r v e d in r a t s

of I

131

. A

th a t w ere

w a s p r o d u c e d b y i n je c tin g

six

T h is w a s a c c o m p a n i e d by an in -

s t a g e s i m i l a r to m e t e s t r u s w a s o b ­
i n j e c t e d w ith s i x r a t - u n i t s o f e s t r a d i o l

b e n z o a t e fo llo w e d a f t e r t w e n t y - f o u r h o u r s b y 0 .4 m i l l i g r a m p r o ­
g e ste ro n e .
I 131.

W hen o v a r i e c t o m i z e d

m illig ra m
in I

131

T h is w a s a c c o m p a n i e d by a d e c r e a s e

p ro g e ste ro n e

u p ta k e .

r a ts w ere

in the u p ta k e of

i n j e c t e d w ith a d o se of 0.4

o n ly t h e r e w a s a s t i l l f u r t h e r d e c r e a s e

S uch a n i m a l s m a y b e c o n s i d e r e d s i m i l a r to r a t s

124
PERCENT

H op pert d ie t

O F I N J E C T E D DOSE O F I 131

P ro e stru s

E stru s

M e te stru s

11.2
±0.9

16.2
±0.7

12.9
±1.6

11.8
±1.0

8.2
±0.6

16.2
±0.7

10.8
±0.7

9.0
± 0 .8

. . . .

R e m in g to n d i e t . . .

D ie s t r u s

Sp ay ed P l u s

R e m in g to n
d i e t ...............

E s tra d io l
B e n z o a te
(6 T .- X J L . )

E stra d io l
B e n z o a te +
0.4 m g.
P ro g e ste ro n e

0.4 m g .
P ro g e ste ro n e

1 6 .8
± o .< ?

11.5
±0.6

10.3
±0.8

C o n tr o l
( spayed )

13.9
±0.5

125
in d i e s t r u s .
In each case the I

131

sig n ific a n tly d iffe re n t f ro m
s t a g e of t h e e s t r o u s

in c re a se d .

w ere

o f th e

ra ts

a l.

a lso

1951)

nor p ro g e ste ro n e

th e u p ta k e of 1

re p o rte d

d u r i n g th e

w as

t h a t a h ig h d o s e of

a l s o w e r e n o t a f f e c t e d b y th e

a lso

re p o rte d

th a t n e ith e r e stro g e n ic

com pounds

an i n c r e a s e

in t h y r o i d w e i g h t w h e n e x p r e s s e d
100 g r a m s

a d m in istra tio n
M o ney e t

c h a n g e d th e t h y r o i d w e i g h t s .
doses

c y c le .

a lo n e o r t o g e t h e r .

of l a r g e

per

131

d i f f e r e n t s t a g e s of th e e s t r o u s

m in istra tio n

g ram s

r a ts w e re in -

u p ta k e .

e stro g e n o r p ro g e ste ro n e

(1 9 5 0 ,

in a c o m p a r a b l e

no s i g n i f i c a n t d i f f e r e n c e s b e t w e e n th e t h y r o i d

The t h y r o i d w e i g h t s
of e i t h e r

p ro g e ste ro n e ,

i n c r e a s e d th e 1 ^ *

T h ere

ra ts

W hen o v a r i e c t o m i z e d

M o n e y e_t a l . (1950)

p ro g e ste ro n e

w e ig h ts

t h a t in n o r m a l

c y c le .

j e c t e d w i th 0 . 8 m i l l i g r a m

uptake in the treated group was not

W ith p r o l o n g e d a d ­

of e s t r a d i o l b e n z o a t e

b o d y w e ig h t.

w e ig h t i s o n ly a r e f l e c t i o n of th e

the

r e s u lt was

in t e r m s

Such an in c r e a s e

of m i l l i ­
in t h y r o i d

s m a l l e r b o d y s i z e of t h i s g r o u p

of r a t s .
A c t u a l l y th e n t h e r e

is n o r e l a t i o n b e t w e e n th e s i z e of th e

th y ro id g la n d and its h o r m o n a l a c tiv ity .
q u o te

V a n d e r l e a n a n d G r e e r (1950):

We w ou ld lik e h e r e

to

''A l t h o u g h h y p e r p l a s i a of the

126
th y ro id g la n d o r d in a r ily a tte n d s

an i n c r e a s e d e fficien c y f o r a c ­

c u m u la tin g io d in e , an d h y p o p la s ia a d e c r e a s e d e ffic ie n c y , fr o m
su ch an e x p e r im e n t s u c h a r e la tio n s h ip

i s d i v o r c e d b e c a u s e , th e

a n im a ls th a t w e r e fe d th io u r a c il b e f o r e h y p o p h y se c to m y a tta in e d
th e l a r g e s t s i z e o f c e l l s

a n d p o s s e s s e d a v e r y lo w c a p a c i t y f o r

io d in e a c c u m u l a t i o n . "
T h e d a t a c o n c e r n e d w ith th e c y c l i c
g la n d a c t i v i t y a s

c o r r e l a t e d to th e e s t r o u s

th e a d r e n a l g l a n d s w e ig h m o r e
th re e

sta g e s,

u n its

(1 m i c r o g r a m )

w e ig h t,

v a r i a t i o n of th e a d r e n a l

(2) a s i n g l e

c y c le

d u r i n g e s t r u s t h a n d u r in g th e o t h e r

i n j e c t i o n of a s

of e s t r a d i o l b e n z o a t e

s m a ll a dose a s

t h a t th e m a x i m a l e x c r e t i o n
d u rin g e s t r u s .

of c o r tic o id s

(4) In th e a b s e n c e

(1952)

a ls o in ­

re p o rted

in g u in e a p i g s w a s

of th e p i t u i t a r y n e i t h e r e s t r o g e n

n o r p r o g e s t e r o n e f a i l e d to e x e r c i s e
a d r e n a l w e ig h t.

p ro g e ste ro n e

Zondek and B u rs te in
ra te

six r a t -

i n c r e a s e d th e a d r e n a l

(3) a d o s e of 0 .2 a n d 0 .4 m i l l i g r a m

c r e a s e d a d r e n a l w e ig h ts.

s h o w e d (1) t h a t

its

e f f e c t on i n c r e a s i n g th e

It is i m p o r t a n t to s t r e s s

th e f a c t t h a t o u r d a t a

a d d a n o t h e r p r o o f to th e f a c t t h a t e s t r o g e n i n d u c e s i t s e f f e c t on
th e a d r e n a l s
Z u ck erm an

t h r o u g h th e p i t u i t a r y ,
(1940).

as

r e p o r te d by B o u rn e and

127
A lth o u g h i t h a s b e e n
th e a d r e n a l g l a n d s

re p o rte d by s e v e ra l in v e stig a to rs th a t

t e n d to e x e r c i s e

r o i d c a p a c i t y to a c c u m u l a t e

I

131

an i n h i b i t o r y e f f e c t o n th e th y -

, fro m

o u r e x p e rim e n ts it a p p e a rs

t h a t th e a d r e n a l i s a l s o e s s e n t i a l f o r n o r m a l t h y r o i d f u n c tio n .
I

131

u p ta k e of th e o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d

n i f i c a n t l y l o w e r t h a n t h a t of r a t s
In th e a b s e n c e
e c to m iz ed

ra ts

r a t s w as

T he
sig ­

t h a t w e r e o v a r i e c t o m i z e d o n ly .

of the a d r e n a l s

th e t h y r o i d g l a n d s of o v a r i -

r e s p o n d e d w ith a h i g h e r u p ta k e of 1

131

to th e

stim ­

u la tin g e f f e c t of a p h y s i o l o g i c a l d o s e of e s t r o g e n th a n t h a t of the
o v a rie c to m iz e d
sam e

dose

ra ts

w ith the a d r e n a l s

of e s t r o g e n .

In c o n c l u s i o n i t s e e m s

t h a t the a d r e n a l g l a n d s a r e e s s e n ­

t i a l f o r th e n o r m a l f u n c t io n of th e
a seco n d ary
reach es

i n t a c t t h a t w e r e g i v e n th e

th y ro id .

It c a n a ls o w o rk a s

s a f e t y c o n t r o l on t h y r o i d a c t i v i t y e s p e c i a l l y w h e n i t

its m a x im a l sta g e .
C o rtic a l h o rm o n es

in d u c e t h e i r e f f e c t on th e t h y r o i d g la n d

e i t h e r b y i n h i b i t i n g th e e f f e c t of TSH a s
e t a l.

(1951) o r b y i n c r e a s e d

u rin e

as

ra te

r e p o r t e d b y W o o d b u ry

of e l i m i n a t i o n of io d in e in th e

r e p o r t e d b y B e r s o n e t a l. (1952) o r p r o b a b l y t h r o u g h e x ­

p a n d in g th e
the s e l e c t i v e

io d id e

space

or

any o th e r m e c h a n is m s n e c e s s a r y fo r

a c c u m u l a t i o n of io d id e b y the t h y r o i d c e l l s .

128
In Hie l i g h t of e l l o f t h e s e

r e s u lts we can s u m m a r is e o u r

h y p o t h e s i s of- th e i n t e r r e l a t i o n s h i p b e t w e e n t h y r o i d , o v a r y , a d r e n a l
a n d p i t u i t a r y of n o r m a l m a t u r e f e m a l e

1.

D u rin g p r o e s t r u s

h y p o a c tiv e c o n d i t i o n .
re le a se d

ra ts

a s f o llo w s :

th e t h y r o i d g la n d i s

U nder th is

in a r e l a t i v e l y

c o n d i ti o n F S H i s p r o d u c e d a n d

r e s u l t i n g i n th e g r a d u a l g r o w t h o f g r a a f i a n f o l l i c l e s , a s

s t a t e d b y R i c h t e r (1933) in th e

r a t , S o l i m a n a n d R e in e k e

(1952)

in th e m o u s e , H o f m e i s t e r (1893) a n d C hu (1944) in th e r a b b i t .
In r a t s
lic le

h y p o th y ro id ism

w i ll e n h a n c e th e e f f e c t i v e n e s s

stim u la tin g h o rm o n e

p h in s a s

as

s t a t e d b y D ane (1935) o r g o n a d o t r o ­

r e p o r t e d b y L e o n a r d (1936), S m e l s e r a n d L e v i n e

a n d J o h n s o n a n d M e i t e s (1 951).
e c to m iz e d

ra ts

w ith e x t r a c t s f r o m

and L is le

2.

P itu ita ry e x tra c ts fro m

w h e n i n j e c t e d in to i m m a t u r e f e m a l e

i n c r e a s e d w e i g h t of th e o v a r i e s
re su lts

of th e f o l ­

(1941),
th y ro id -

m ice

caused

a n d u t e r i w hen c o m p a r e d to th e

n o rm al

a n im a ls, as

r e p o r t e d b y S te in

(1942).

D u rin g e s t r u s

e n o u g h to s t i m u l a t e

e s t r o g e n is p r o d u c e d in a m o u n t s l a r g e

t h y r o i d a c t i v i t y v i a th e p i t u i t a r y .

In creased

t h y r o i d a c t i v i t y i s b e l i e v e d to f a v o r th e p r o d u c t i o n of LH .
(1930) a n d W e i c h e r t a n d B o y d (1933)

r e p o r te d th a t fe e d in g

W e ic h ert
ra ts

129
w ith d e s i c c a t e d t h y r o i d p r o l o n g s
to t w e n t y - f o u r d a y s .

T h ere

the d i e s t r u s p e r i o d f r o m

th irte e n

w e re p e r s i s t e n t fu n c tio n a l c o r p o r a

lu te a su g g e stin g

in c re a se d

th y ro id h o rm o n e

a l s o m i g h t h a v e a d i r e c t e f f e c t on th e o v a r y

1925;

T y n d a le a n d L e v i n ,

r o x i n e io d in e

is f i x e d

in

o u t p u t of the l u t e i n i z i n g h o r m o n e .

1937).

S a lte r

(1949)

tw o g e n e r a l l o c a t i o n s .

a c c u m u l a t i o n in th e p i t u i t a r y

and o v ary .

c u m u l a t i o n in th e p e r i p h e r a l

tissu e s, p rim a rily

A lle n (1939)
tia te d by th y ro x in e

s u g g e s te d th at changes
as

w e ll

The

is

a lso

a

The f i r s t i s
second is its
the

sta g e

of th e t h y r o i d g l a n d ,

such

its
ac­

sk e le ta l m u sc le .

in th e f o l l i c l e

are

in i­

a s b y the m a t u r a t i o n h o r m o n e of th e

s a fe ty m e c h a n ism

la te d a d re n a l a t th is

(L ee,

s t a t e d t h a t th e t h y ­

a n t e r i o r p i t u i t a r y b u t t h a t th e l a t t e r o n ly p r o d u c e s
T here

T he

ru p tu re .

in d u c e d b y th e

stim u ­

to p r e v e n t o r l i m i t th e o v e r a c t i v a t i o n
an e f f e c t i s a l s o in d u c e d v i a th e

sam e

h ig h w a y , th e p i t u i t a r y .

3.

D u r in g m e t e s t r u s

s lo w e d d o w n a n d p r o g e s t e r o n e
am o u n ts.
creases.

U nder th e se

th e r a t e of s e c r e t i o n of e s t r o g e n

i s p r o d u c e d in g r a d u a l l y i n c r e a s i n g

c o n d itio n s th y ro id a c tiv ity g ra d u a lly

de-

is

130

4.

D u rin g d ie s tr u s p r o g e s te r o n e p re d o m in a te s o v e r e s t r o ­

gen r e s u ltin g

in d e c r e a s e d t h y r o i d a c t i v i t y .

n o t m e d i a t e d v i a th e p i t u i t a r y .

T h is m e c h a n i s m

is

I t m a y b e due t o a d i r e c t e f f e c t

o f p r o g e s t e r o n e o n th e t h y r o i d o r m o s t p r o b a b l y b y e x p a n d in g th e
io d id e s p a c e .

T h o rn e

e t al.

(1938)

c r y s t a l l i n e p r e p a r a t i o n s of e s t r o n e
r e te n tio n of s o d iu m , c h lo r id e
fo re , it s e e m s

space

and p ro g e ste ro n e

i n d u c e d th e

a n d w a t e r in n o r m a l d o g s .

th a t p ro g e s te ro n e

th e e x t r a c e l l u l a r

r e p o r t e d t h a t th e i n j e c t i o n of

and a ls o e s tro n e

of th e b o d y ,

T h ere­

c o u ld e x p a n d

a n d c o n s e q u e n t l y th e

io d id e

space.

5.

A g a in , in p r o e s t r u s ,

a r e p r o d u c e d a t h ig h l e v e l s ,
g la n d ,

re su ltin g

a n d th e c y c l i c v a r i a t i o n s

6.

L arg e

1951).

th y ro id

s ta r t o v er.

o u r e x p e rim e n ts

(1950 a n d

to w h a t o c c u r s

i n a h y p o a c tiv e

a m o u n t s of p r o g e s t e r o n e

a s p o in te d out f r o m
M on ey e t a l .

n e ith e r e stro g e n n o r p ro g e ste ro n e

T hese

d u rin g p re g n a n c y .

in c re a se

and fro m
c o n d itio n s

th e

th y ro id a c tiv ity
re p o rts

m ay be

of

sim ila r

SU M M A R Y AND C O N C L U SIO N S

1.

D e te rm in a tio n s

te m p e ra tu re

w ere

m a d e of ox y g en c o n s u m p tio n , b a s a l

a n d b o d y w e i g h t s of r a t s

u n d e r b a s a l co n d itio n s d u rin g

*

th e f o u r s t a g e s

of th e e s t r o u s

c y c le .

I t w a s found th a t t h e r e

s ig n ific a n tly i n c r e a s e d o x y g en c o n s u m p tio n d u rin g e s t r u s .

is

T here

w e re no s ig n ific a n t d if f e r e n c e s b e tw e e n b a s a l te m p e r a tu r e s o r body
w e i g h t s a t th e f o u r

2.
d u r in g th e

T he

a tta in s

u p ta k e by th e

S im ila r

show ed th a t th e re

is

a n i n c r e a s e d u p ta k e
and

and p r o e s tr u s .

c y c le

t h a t o f th e

s h o w e d a p a t t e r n of c y c l i c v a r i a ra t.

The m a x i m a l u p ta k e of I

a t t a i n e d b y th e t h y r o i d s of p r o e s t r o u s

A sin g le

at m e te stru s

s t u d i e s o f l l 31 u p t a k e b y th e t h y r o i d g l a n d s of

d u r i n g th e e s t r o u s

4.

th y ro id g la n d s of r a t s

T he u p ta k e g r a d u a l l y d e c r e a s e s

tio n d i f f e r e n t f r o m
is

c y c le

131

its lo w e s t le v e l d u rin g d ie s tr u s

3.
m ic e

stu d y of I

e stro u s

d u rin g e s t r u s .

s t a g e s o f th e e s t r o u s c y c l e .

i n j e c t i o n of 6 o r

b en zo ate

i n c r e a s e d th e

a f t e r th e

e s tr o g e n in je c tio n .

300

s i x - h o u r u p ta k e
T here

m ic e .

r a t - u n i t s of e s t r a d i o l

of I

w ere

131

131

fo rty -e ig h t h ours

no d i f f e r e n c e s b e t w e e n

132
th e e f f e c t* o f th e tw o d o s e s o n t h y r o i d u p ta k e , w ith th e c o n c l u s i o n
t h a t th e d o s e of e s t r o g e n i s n o t v e r y c r i t i c a l .

5.

T h e a d m i n i s t r a t i o n of t e n d o s e s of 300 r a t - u n i t s

e s t r a d i o l b e n z o a t e on a l t e r n a t i v e

d a y s d id n o t c h a n g e th e I

of
131

u p ta k e b y th e t h y r o i d s w h e n c o m p a r e d to c o n t r o l s .

6.

A s i n g l e d o s e of 0 .2 o r 0 .4 m i l l i g r a m

of p r o g e s t e r o n e

d e c r e a s e d th e u p t a k e of 1*^* b y th e t h y r o i d s w h ile a d o s e of 0 .8
m illig ra m

i n c r e a s e d th e u p ta k e .

7.

T he i n j e c t i o n of 0 .4 m i l l i g r a m

of p r o g e s t e r o n e c o u n ­

t e r a c t e d th e e f f e c t of e s t r o g e n o n t h y r o i d f u n c tio n w ith th e n e t
r e s u l t of a d e c r e a s e d I

8.

131

u p ta k e .

E x p e r i m e n t s on h y p o p h y s e c t o m i z e d - o v a r i e c t o m i z e d r a t s

show ed th a t e s t r o g e n p r o d u c e s

its

stim u la tin g

e f f e c t on th e t h y r o i d

g la n d v i a th e p i t u i t a r y gland, .s in c e e s t r o g e n d id n o t c h a n g e th e
I

131

u p ta k e

9.

in h y p o p h y s e c t o m i z e d r a t s .

P ro g e ste ro n e

d e c r e a s e d th e u p ta k e of I

r o i d g l a n d s of h y p o p h y s e c t o m i z e d r a t s ,
in d u c e i t s

131

b y th e t h y ­

sh o w in g t h a t i t d o e s n o t

e f f e c t m a i n l y v i a th e p i t u i t a r y .

It m i g h t h av e a d i r e c t

e f f e c t on th e t h y r o i d o r a c t b y s i m p l y e x p a n d in g th e io d id e

space.

133
10.
ra ts

An e x p e r i m e n t w ith o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d

s h o w e d t h a t th e a d r e n a l g l a n d s

seem

to b e e s s e n t i a l f o r

n o r m a l t h y r o i d f u n c t i o n a s i n d i c a t e d b y th e d e c r e a s e d I
of th e o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d

ra ts

131

u p ta k e

w h e n c o m p a r e d to

o v a r i e c tom s z e d r a t s .

11.

The 1

131

u p ta k e by th e t h y r o i d g l a n d s o f o v a r i e c t o -

m iz e d -a d re n a lc c to m iz e d
th a n t h a t of r a t s

ra ts

t r e a t e d w ith e s tr o g e n w as h ig h e r

w ith t h e i r a d r e n a l s i n t a c t b u t g iv e n th e

d o s e of e s t r o g e n .

T h e a d r e n a l g l a n d s o f th e

a n im a ls w e re h e a v ie r th an c o n tr o ls ,
w h e n th e a d r e n a l g l a n d s a r e
tra tin g
w ere

e stro g e n -tre a te d

g iv in g th e i m p r e s s i o n t h a t

stim u la te d i t d e c r e a s e s

c a p a c i t y of th e t h y r o i d f o r i o d i n e m o r e

th e c o n c e n ­

th a n if th e a d r e n a l

a b se n t.

12.
a n d b lo o d

The th y ro tro p h ic h o rm o n e
sera

of th e

ra ts

c o n t e n t of th e p i t u i t a r i e s

k ille d a t th e fo u r

c y c l e , w e r e a s s a y e d u s i n g th e u p ta k e of P
a n i n d e x of t h y r o i d r e s p o n s e
The th y ro tro p h ic

sta g e s

h o r m o n e c o n t e n t of th e

of th e c y c l e .

32

s t a g e s of th e

e stro u s

b y c h ic k t h y r o i d s

to th e t h y r o t r o p h i c

s e e m e d to be h i g h e r th a n t h a t of th e
th re e

sam e

seru m

se ra fro m

as

h o r m o n e p o te n c y .
of e s t r u s
ra ts

a n im a ls

a t th e o t h e r

134
13.

T h e r e w e r e no s i g n i f i c a n t d i f f e r e n c e s b e tw e e n the

th y ro id w e ig h ts

of r a t s

or m ic e

a t th e f o u r s t a g e s of th e e s t r o u s

c y c le .

14.

A sin g le

d io l b e n z o a t e

15.

P ro lo n g e d

of m i l l i g r a m s

per

w e ig h t of th e

ra ts.

16.

in d i e s t r u s

w ere

e stru s

w ere

o n ly w hen e x p r e s s e d in t e r m s

T h e a d r e n a l w e ig h t s w e r e h e a v i e r d u r in g
a ll o t h e r

w ere

sta g e s

of the c y c le .

no s i g n i f i c a n t d i f f e r e n c e s b e tw e e n the

of r a t s

In r a t s

18.

of e s t r a ­

100 g r a m s b o d y w e ig h t, due to th e l i g h t e r body

T here

k ille d d u r i n g

300 r a t - u n i t s

a d m i n i s t r a t i o n of 300 r a t - u n i t s of e s t r a d i o l

th y ro id w eig h ts

d u rin g

p itu ita ry w e ig h ts

17.

6 or

d id n o t h a v e an a f f e c t on th e t h y r o i d w e ig h ts .

b e n zo ate i n c r e a s e d

e s t r u s th an

d o s e of e i t h e r

a t th e f o u r

s t a g e s of the c y c le .

th e o v a r y w e i g h t s of th e a n i m a l s

k ille d when

s i g n i f i c a n t l y h e a v i e r t h a n th o s e of a n i m a l s

p ro e stru s.

In

ra ts

th e u t e r u s

w e i g h t s of the a n i m a l s k ille d d u rin g

s i g n i f i c a n t l y h e a v i e r th a n th o s e of the a n i m a l s

d u r in g th e o t h e r

th re e

sta g e s

of th e c y c le .

k ille d

135

19.

In th e l i g h t o f a l l th e a f o r e m e n t i o n e d r e s u l t s ,

a hy­

p o t h e s i s w a s p r e s e n t e d to e x p l a in th e p o s s i b l e ^ .re la tio n s h ip b e tw e e n
th e t h y r o i d , o v a r y , a d r e n a l ,

and p itu ita ry .

B IB L IO G R A P H Y

A l b e r t , A.

1952.

A lb e rt, A .,

a n d T e n n e y , A.

and

T h y r o i d G la n d .
1951.

T h y r o x i n e on the

A n n . R e v . P h y s i o l . 1 4 :4 8 1 -4 9 8 .
E f f e c t of I o d id e ,

T h io u ra c il

D i s a p p e a r a n c e of T h y r o i d a l I 131.

P r o c . s o c . E x p t . B i o l , a n d M e d . 7 7 :2 0 2 - 2 0 3 .
A lb e rt, A .,

T e n n e y , A ., a n d F o r d , E .

tiso n e

T he E f f e c t of C o r ­

a n d C o r t i c o t r o p i n o n the B io lo g ic

R a d io io d in e .
A lle n , E .

1952.

1939-

D e c a y of T h y r o i d a l

E n d o c r i n o l o g y 5 0 :3 2 4 - 3 2 6 .

" S e x and In te rn a l S e c r e tio n s ."

W illia m s

and

W ilk in s, B a ltim o r e .
A lle n ,

E .,

S m it h , G.

M ., a n d G a r d n e r ,

W. U.

1937.

A cc en tu a tio n

o f th e G r o w th E f f e c t of The e l in on G e n i t a l T i s s u e s of th e
O v a r i e c t o m i z e d M o u s e b y A r r e s t of M i t o s i s w ith C o lc h i c i n e .
A m er.
A ndersen,

J o u r . A n a t.

6 1 :3 2 1 - 3 4 1 .

D. H ., a n d - K e n n e d y , H. S.

o lo g y o f R e p r o d u c t i o n .
o f th e F e m a l e

1932.

S tu d ie s on th e P h y s i ­

IV. C h a n g e s in th e A d r e n a l G la n d

R a t A s s o c i a t e d w ith th e O e s t r u s

J o u r . P h y s i o l . 7 6 :2 4 7 - 2 6 0 .

C y c le .

137
A ndersen,

D. H ., a n d K e n n e d y , H. S.

e c t o m y o n th e A d r e n a l ,

1933.

T he E f f e c t of G o n a d -

T h y r o i d a n d P i t u i t a r y G la n d s .

Jo u r.

P h y s i o l . 7 9 :1 - 3 0 .
A s tw o o d ,

E . B.

nancy.

1951.

T he U se of A n t i t h y r o i d D r u g s D u r in g P r e g ­

J o u r . C lin . E n d o c rin o lo g y

B a k e r , B. L.., a n d E v e r e t t , N. B.

1 1 :1 0 4 5 -1 0 5 6 .

1947.

The E f f e c t of D ie th y l -

s t i l b e s t e r o l on the A n t e r i o r H y p o p h y s is of T h y r o i d e c t o m i z e d
R a ts.
B arm an ,

J.

E n d o c r i n o l o g y 4 1 :1 4 4 - 1 5 7 .
M

1940.

R ab b its
r o id .

F a c to rs

In flu e n c in g th e S e n s i t i v e n e s s of

to G o n a d o tr o p h i c E f f e c t of G r a v i d U r in e a n d T h y ­
R e v . S o c . A r g e n t i n i a B i o l . 1 6 :4 6 0 -4 6 5 .

B aum ann, E. J .,

a n d M a r i n e , D.

C o r t e x in R a t s

1945.

I n v a lu tio n of th e A d r e n a l

F e d W ith T h i o u r a c i l .

E n d o c r i n o l o g y , 36:

400-405.
B e n e d i c t , F . G ., a n d F i n n , M. D.
G aseous

M e ta b o lism .

1928.

N o rm a l M e n s tru a tio n and

A m e r. Jo u r.

B e r s o n , S. A ., a n d Y a lo w , R. S.

1952.

P h y s i o l . 8 6 :5 9 -6 9 .

T he E f f e c t of C o r t i s o n e

o n the Io d in e A c c u m u l a t i n g F u n c t i o n of th e
in E u t h y r o i d S u b j e c t s .
1 2 :4 0 7 -4 2 2 .

T h y r o i d G la n d

J o u r . C l i n . E n d o c r in o lo g y a n d Me t a b .

138
B e s f o r d , H ., C r o o k e , A. C ., a n d M a th e w s , J .
A ssay for
c rin o lo g y .
B in g , R.

1928.

T h y ro tro p h ic H orm one

D.

U sin g P

1952.
32

C h ic k

J o u r. Endo­

8:X V.
U ber P e rio d is c h e H y p o th y re o se .

E n d o k rin o lo g le .

2 :3 2 1 - 3 3 0 .
B la x te r,

K. L .

194 5.

The P r e p a r a t i o n a n d B i o l o g i c a l E f f e c t s

of

lo d in a te d P r o t e i n s .

The E f f e c t of I o d i n a t e d P r o t e i n F e e d ­

in g on th e E a c t a t i n g

Cow.

B lu n t, K ., a n d D y e, M.
W om en.
B o tk in , A. L..,

1921.

J o u r . E n d o c r i n o l o g y . 4 :2 3 7 - 2 6 5 .

B a s a l M eta b o lism

of N o r m a l

J o u r . B i o l . C h e m . 1 5 7 :6 9 -7 3 .
a n d J e n s e n , H.

1951.

on C o n te n t a n d C o n v e r s i o n of
th e

Rat

T h y r o id .

Fed.

B o tk in , A.

L..,

a n d J e n s e n , H.

E ffe cts

of V a r i o u s H o r m o n e s

R a d io a c ti v e Io d in e (I

) in

P r o c . 10:164- 165.
1952.

The E f f e c t of E p i n e p h r i n e

a n d T h y r o t r o p i n on T h y r o i d F u n c t i o n in R a t s .

E n d o c r i n o lo g y

5 0 :6 8 - 7 2 .
B o u r n e , G .,

and

Z u ck erm an ,

S.

1940.

C hanges

in R e l a t i o n to th e N o r m a l a n d A r t i f i c i a l
C y c le
B rad b u ry , J.

in th e R a t.
T.

A n te rio r

1947.
P itu ita ry

Jo u r.

in th e A d r e n a l s
T h re sh o ld O e s tru s

E n d o c r in o lo g y 2 :2 8 3 -3 1 0 .

O v a r i a n I n f lu e n c e on th e R e s p o n s e of th e
to E s t r o g e n s .

E n do c r i n o lo g y 4 1 :5 0 1 - 5 1 3 .

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B r e n e m a n , W. R.

1941.

G r o w th of th e E n d o c r i n e G la n d s an d

V i s c e r a in th e C h ic k .
B r i m b e r g , J . , H a s s , N. H .,
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M o d e ra te

E n d o c r i n o lo g y 2 8 :9 4 6 - 9 5 4 .
D r i m e r , M. G ., a n d W e it z m a n , C. C.

D o s e s of E s t r o g e n a n d T h y r o i d in th e

P r e v e n t i o n of A b o r t i o n .

N ew Y o r k S ta te J o u r . M e d . $1:

6 2 3 -6 2 5 .
B robeck, J.

R ., W h e a tla n d , M ., a n d S t r o m i n g e r , J , L .

V a ria tio n

1947.

in R e g u l a t io n of E n e r g y E x c h a n g e A s s o c i a t e d

w ith E s t r u s , D i e s t r u s

a n d P s e u d o p r e g n a n c y in R a t s .

Endo­

c rin o lo g y 4 0 :6 5 -7 2 .
B r o d y , S., a n d F r a n k e n b a c h , R. F .
E n ergy

M e ta b o lism

1942.

Age C h a n g e s in S iz e ,

a n d C a r d i o - R e s p i r a t o r y A c t i v i t i e s of

T h y ro id e c to m iz e d C a ttle .

M o. A gr. E x p t. S ta .

R e s. B u ll.

349.
C a m e r o n , G. R ., a n d A m i e s .
F e e d i n g o n th e

E stru s

A. B.

1926.

T he E f f e c t of T h y r o i d

C y c le of the G u in e a P i g

a n d M o u se .

A u s t r a l . J o u r . E x p t . B i o l , a n d M e d . S c i . 3 :3 7 -4 3 .
C a r t e r . G. S.

1932.

Io d in e

C om pounds and F e r tiliz a tio n .

P h y sio lo g ic a l P r o p e r tie s
of E c h i n u s e s c u l e n t u s .

VI.

of E x t r a c t s of O v a r i e s a n d T e s t e s
J o u r . E x p t . B i o l . 9 :2 5 3 - 2 6 3 .

C h o u k e , K. 3.

1930.

T h e E f f e c t of C a s t r a t i o n on th e P r o l i f e r a t i v e

A c t i v i t y a n d S t r u c t u r e of th e
E n d o c rin o lo g y

1 4 :1 2 - 1 6 .

C h o u k e , K . S ., F r i e d m a n ,
A c t i v i t y of th e

H ., a n d L.oeb, L .

J.

P.

1944.

P ro life ra tiv e

A n a t . R e c o r d 6 3 :1 3 1 - 1 3 7 .

I n f lu e n c e of th e

G o n a d o tro p h ic

1935.

T h y r o i d G la n d of th e F e m a l e G u in e a P i g

D u r i n g th e S e x u a l C y c l e .
Chu,

T h y r o i d G la n d in G u in e a P i g s .

T h y r o i d G la n d on th e P i t u i t a r y

H o r m o n e A c t i v i t y in th e

R a b b it.

E nd o c rin ­

o lo g y 3 4 :9 0 - 1 0 2 .
Chu,

J.

P .,

a n d You, S. S.

and E stro g e n

194 5.

in th e R e g u l a t i o n of G o n a d o tr o p h ic A c tiv ity

of th e A n t e r i o r P i t u i t a r y .
C o n k lin ,

C. J . ,

R a te

T h e R o le of T h y r o id G la n d

a n d M c C lin d o n , J .

in R e l a t i o n

J o u r . E n d o c r in o lo g y 4 :1 1 5 - 1 2 4 .
F.

1930.

The B a s a l M e ta b o lic

to the M e n s t r u a l C y c l e .

A r c h . Int.

M ed.

45: 1 2 5 -1 3 5 .
C u tu ly ,

E.

1941.

P itu ita ry

S t u d i e s on the H i s t o l o g y a n d P h y s io lo g y of the
of th e

c rin o lo g y
D a C o sta ,

E .,

T r e a t e d w ith P r o g e s t e r o n e .

Endo-

2 9 :6 9 5 - 7 0 1 .

a n d C a r l s o n , A. J .

D e sic c a te d
R a t.

R a ts

1933.

T h e E f f e c t of F e e d i n g

T h y r o i d Upon th e S e x u a l M a t u r i t y of the A lbin o

A m e r . J o u r . P h y s i o l . 1 0 4 :2 4 7 -2 5 2 .

141
D 'A m o u r ,

T. £ .

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m i n i n g th e

C o m p a r i s o n o f M e th o d s

T i m e o f O v u l a ti o n .

U s e d in D e t e r *

J o u r . C l i n . E n d o c r in o lo g y

3 :4 1 - 4 8 .
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C h a n g e s in C i r c u l a t i n g

E o s i n o p h i l s in W o m en D u r i n g th e M e n s t r u a l C y c le a n d R e ­
p ro d u c tio n .

J o u r . C l i n . E n d o c r in o l o g y 9 :7 1 4 - 7 2 4 .

D e s c l i n , L . , a n d E r m a n s , A.
F o llic u la ire
C hez le

sur

R at.

D o u g h e rty , J ., G r o s s ,

L 'A c tiv ite

A. W.
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Em ge,

1938.

311-329.

J .,

T.

de L 'H y p o p h y s e

C. P .

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S te a d y S ta te

E nd o c r i n o l o g y 4 8 :7 0 0 - 7 1 3 .

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and T h y ro id F u n c tio n ,

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-—
L acueur.

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M orphologic O v a r ia n

Thyrohype rp la stic
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(E nglish

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\cta.

d ie

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M ahom er,

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14 :4-o.

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in E n v i r o n m e n t a l

E xperim entelle

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K l ir i . W c lin sc h r .

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T em perature

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160:2 5 3-25 8.
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A ttem pts

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T em perature
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in I m m a t u r e

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E . , a n d W e r t z , A.

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A ction.

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C o u r b e de

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T em perature

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305-307.
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W. L . , K i r s c h n e r ,
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P roducts

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on the

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M errill, P .,

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E f f e c t s of A d r e n a l a n d G o n a d a l

W eight and R adioiodine

T h y r o i d G l a n d in the R a t.
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L>.,

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The

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1 9 3 2 (a ).

E x p e r i m e n t a l S tu d y of th e

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N akam ura,

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E x p e r i m e n t a l Study of the

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T h y r o p r o t e i n a n d T e s t o s t e r o n e P r o p i o n a t e o n G r o w t h a nd
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of P r o t e i n

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T h y r o id e c to m y .

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E x is tin g In fo r m a tio n "
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P a s c h k i s , K ., C a n ta ro w , A ., and P e a c o c k ,
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T h y r o i d F u n c t i o n in t h e A l a r m

Reaction.

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Payne, F .

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Fow l.
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A nterior P itu itary

A nat. R ecord
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T h y r o i d R e l a t i o n s h i p i n the

8 8 :3 3 7 - 3 5 0 .

of G o n a d R e m o v a l on the A n t e r i o r P i ­

t u i t a r y of t h e F o w l f r o m
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t h i o u r a c i l on th e

Perry,

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T h e A c t i o n of C o r t i s o n e

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A d r e n a l G la n d s a n d C h e m i s t r y ,

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Investiga­

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t r o p h i n a n d G o n a d o t r o p h i n P r o d u c t i o n in th ^ R a t P i t u i t a r y
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