DIFFERENCES IN THYROID ACTIVITY OF SEVERAL STRAINS
OF INBRED AND F., HYBRID MICE
1

by
ABOLGHASSEM AMIN

AN ABSTRACT
Submitted to the School for Advanced Graduate Studies
Michigan State University of Agriculture and
Applied Science in partial fulfillment of
the requirements for the degree of
DOCTOR OF PHILOSOPHY
Department of Physiology and Pharmacology
Year

Approved

1956

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1

ABOLGHASSEM AMIN

ABSTRACT

Strain differences in thyroid function were studied
in A/Jax, BALB/c, C57BR/cd, C57BL/6 mice and their
brids, CAF1 (BALB/c 9 x A/Jax
C57BR/'cd <?) •

hy­

i ) and BBFX (C57BL/6 ? x

These strains of mice were provided from the

Jackson Memorial Laboratory and were produced by brother x
sister matings for more than 20 generations and are, there­
fore, considered to be quite homogeneous.
Radioiodine uptake, its turn-over rate and the thy­
roid secretion, which involves the determination of the
amount of 1-thyroxine required to prevent output of iodine
from the thyroid of individual mice previously given 5
microcuries of 1-131, were estimated.
Statistically significant differences between sexes
in either of the parameters measured, except in C57BR/cd
strain, were not found.

The average per cent 1-131 uptake

and per cent output, respectively, for the various geno­
types were:

A/Jax 16.1, 15*3; BALB/c 17*4, 18.0; CAF^

19.4, 13.8; C57BR/cd 10.4, 26.0; C57BL/6 7-9, 34.1; and
BBF^ 10.4, 32*3-

Fer cent uptake was significantly higher

and output rate was significantly lower in the first three
groups than in the others.

The thyroid secretion values

were 2.09, 1.77; 2.36, 1.76; 2.07, 1.65; 3.67, 3.04; 3-97
and 2.85 For the males and females of strains A/Jax, CAF^,
BALB/c, C57BR/cd, BBF^ and C57BL/6, respectively.

ABOLGHASSEM AMIN

ABSTRAC

A reciprocal relationship was observed between the
per cent uptake and the output rate.

The results clearly

show the strain differences among the strains studied.
Although these data do not indicate the number of
genetic factors involved in control of thyroid secretion
level, they provide strong evidence that it is a heritable
character.

DIFFERENCES IN THYROID ACTIVITY OF SEVERAL STRAINS
OF INBRED AND F

HYBRID MICE

By
ABOLGHASSEM AMIN

A THESIS
Submitted to the School for Advanced Graduate Studies
Michigan State University of Agriculture and
Applied Science in partial fulfillment of
the requirements for the degree of
DOCTOR OF PHILOSOPHY
Department of Physiology and Pharmacology
1956

ACKNOWLEDGMENT
The author wishes to express his sincere apprecia­
tion to Dr. E. P. Reineke for his stimulating guidance and
helpful criticism throughout the course of this investiga­
tion.
Special thanks are due to Dr. C. K. Chai, Jackson
Memorial Laboratories, Bar Harbor, Maine, for his active
collaboration in the research.
The aid of Dr. William D. Baten in the statistical
analysis of these data is gratefully acknowledged.
The author wishes to express his gratitude to Mr.
Jack Monroe and Mr. Howard Hardy for their help and to Dr.
Ellen J. Monkus for her technical assistance.
Thanks are due to Dr. B. V. Alfredson for the use of
the facilities of the Department of Physiology and Pharma­
cology and to the Michigan Agricultural Experimental Sta­
tion for support of the project under which this work was
done.

TABLE OF CONTENTS
PAGE
REVIEW OF LITERATURE ................................

1

OBJECTIVES AND EXPERIMENTAL APPROACHES ..............

6

Materials and Methods

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

7

Measurement of 1-131 uptake, output rate con­
stant and thyroid hormone secretion rate . . . .

10

I. 1-131 u p t a k e ..............................

10

II. Measurement of output rate constant

....

10

III. Determination of the thyroid hormone se­
cretion rate by injection of 1-131 and
exogenous thyroxine ....................

11

R E S U L T S ............................................

15

Heterozygous M i c e ................................

15

Radioiodine uptake values

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

15

Determination of per cent output per day and
biological half-life ..........................

18

Measurement of thyroid secretion rate of hetero­
zygous m i c e ............

23

Mice of Inbred Strains and Their F^ Hybrids

....

Radioiodine u p t a k e ............

25
25

Measurement of output rate c o n s t a n t ............... 25
Measurement of thyroid secretion rate in inbred
mice and their F^ h y b r i d ............

30

DISCUSSION..........................................

35

SUMMARY AND CONCLUSIONS

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

41

BIBLIOGRAPHY ........................................

44

AP P E N D I X ............................................

51

LIST OF TABLES
TABLE
I.

Average per cent 48-hour uptake and their
standard errors in mice from Carworth
Farms . . . ...................................

II.

24-hour and 48-hour uptake of mice from
Michigan State Health Laboratory
...........

III.

Average per cent outputs per day and their
standard errors in mice from Carworth
Farms
................... ............

IV.

The average I-1J.1 uptake in terms of per cent
of injected dose in two males and two fe­
males in each genotypic group at different
times after 1-131 injection .................

V.

Average percentage of both 1-131 uptake and
output rate constant in each genotypic
group of mice ................................

VI.

Thyroid secretion rate of inbred and F, hy­
brid mice . . . ..............................

APPENDIX
TABLE
I.

Trial 1. The
values obtained for the per
cent of injected dose, the per cent output
per day and the biological half-life for
each individual mouse of the Carworth
strain
. . . .................................

II.

Trial 2. The values obtained for the per
cent of injected dose, the per cent output
per day and the biological half-life for
each individual mouse (Carworth)
...........

III.

Trial 3. The values obtained for the per
cent of injected dose, the per cent output
per day and the biological half-life for
each individual mouse (Carworth)
...........

V

APPENDIX
TABLE
IV.

V.

VI.

VII.

VIII.

IX.

PAGE

Trial 4. The values obtained for the per
cent of injected dose, the per cent output
per day and the biological half-life for
each individual mouse(Carworth)
. .........

55

Trial 5* The values obtained for the per
cent of injected dose, the per cent output
per day and the biological half-life for
each individual mouse (Garworth)
...........

56

'Trial 6. The values obtained for the per
cent of injected dose, the per cent output
per day and the biological half-life for
...........
each individual mouse (Carworth)

57

desuits of analysis of variance of 1-131 up­
take among genetically different groups of
mice at 48 hours after i n j e c t i o n ..........

58

Results of analysis of variance of 1-131 out­
put rate constant among genetically differ­
ent groups of m i c e ........................

59

Results of analysis of variance of thyroid
secretion rate among genetically different
groups of m i c e ............................

60

LIST OF FISURFS
FIGURE

FAGE

% uptake of 1-131. . . .

1.

Distribution of 48 hour

2.

Distribution of biological half-life

..........

22

3.

Relationship between 1-131 uptake and the
biological half-life ........................

24

Average percentage of I-13I uptake and rate
of turn-over in six genetically different
strains of m i c e ..............................

28

3. Log percentage of 1-131 uptake with respect
to time following injection in mice from
four different inbred strains ................

29

4.

6.

Thyroid secretion rate of inbred and the
hibrid m i c e ..................................

19

33

APPENDIX
FIGURE
1.

Loss of the activity of carrier-free 1-131
standard in counts per minute, drawn on
semi-log scale against time in d a y s ..........

61

2-10.

Thyroid secretion rates of heterozygous
m i c e ...................................... 62-70

11-21.

Thyroid secretion rates of inbred mice
and their F^ h y b r i d s ...................... 71-81

REVIEW OF LITERATURE
Iodine was discovered in the thyroid gland in 1896
by Baumann (1), and the ability of the gland to absorb io­
dine selectively from the blood in relatively large amounts
was demonstrated in 1913 and 1916 by Marine and his asso­
ciates (2,3,4-,5).

Since then the importance of iodine in

thyroid metabolism has been amply demonstrated.
The purely chemical investigation of iodine and its
compounds in the thyroid has yielded outstanding results,
culminating in the isolation (6), chemical identification
and synthesis of the active principles of the thyroid
gland, namely, thyroxine by Harrington and his coworkers
(7,8>9) and triiodothyronine by Gross and Pitt-Rivers (10,
11,12).
Physiologically, the relationship which exists be­
tween the thyroid and the anterior lobe of the hypophysis
(13,14) plays a major role upon thyroid function.

The an­

terior pituitary secretes a hormone called thyrotropin or
the thyrotropic principle (13), which regulates iodine
trapping (13,16,17,18,19,20,21), its organic binding and
its release into the circulation (22).
These different phases of the iodine cycle are inter­
dependent, but can be classified into:

1) iodine trapping,

2
2) incorporation of iodine into organic binding, and 3) re­
lease of the thyroid hormone.
Before goitrogenic compounds were discovered, thy­
roidal activity was measured by such methods as measurement
of oxygen-carbon dioxide exchange (23,24,23), rate of meta­
morphosis in tadpoles, or by chemical methods such as the
estimation of the protein-bound iodine in the thyroid gland
or the blood plasma (26,27,28,29).

When goitrogenic compounds became known, another
technique for measuring the thyroid secretion was added to
those already present.

Goitrogens inhibit the formation of

the thyroid hormone, which permits increased secretion of
TSH by the pituitary; this in turn stimulates the thyroid
and causes hypertrophy and hyperplasia of the gland (30,31,
32,33)*

Enlargement of the thyroid can be prevented by the

administration of thyroxine in sufficient amounts to bring
the pituitary and thyroid back into normal balance.
Dempsey and Astwood (34-) observed that the decrease
in thyroid weight in thiouracil-treated rats given thyrox­
ine bore a quantitative relation to thyroxine dosage.

The

relationship between thyroid weight and thyroxine dosage is
a straight line.

The point where the response curve inter­

cepts the normal thyroid weight represents the amount of
thyroxine required to maintain the normal thyroid pituitary
balance.

3
In recent years the thyroid secretion rate has been
measured in several species of animals.

Of special inter­

est are the findings by Hurst e_t al. (35) that three
strains of mice showed differences in thyroid secretion
rate.

They demonstrated that Schwing female mice had the

highest thyroid secretion rate, whereas Rockland and G^H
females had almost the same secretion rate.

Kixner et al.

(36), Schultze and Turner (37) and Mixner and Upp (38) ob­
served differences in the thyroid secretion rates of sev­
eral strains of chickens.
With the discovery of artificial radioactivity by
Joliot and Curie (39), the building of the cyclotron (40,
41) and the development of the uranium chain reacting pile
(42), a valuable tool became available to biologists.
In 1937, a cooperative investigation for the study
of thyroid physiology with radioactive isotopes of iodine
was started (43).

Since then the isotopes of iodine, and

especially 1-131 with 8-day half-life, have been used in
the study of thyroid gland physiology.
Shortly after radioactive iodine is administered it
is trapped by the thyroid gland, and incorporated into or­
ganic binding in the same way as stable iodine.

The amount

of iodine which is collected by the thyroid gland at a certain
time after its administration is called iodine uptake.
Thyroid uptake is one expression of the gland1s capacity to

4
manufacture its hormone.

The thyroid uptake is controlled

at least in part by the anterior pituitary (4-4,45).

One

should bear in mind, however, that the 1-151 uptake is of
value on a comparative basis only when all other factors
such as the amount of iodine intake in food, age and envi­
ronmental temperature remain the same.
After the maximum uptake is reached, which usually
depends on the species of animal, 1-151 concentration in
the thyroid declines exponentially.

The decrease in radio­

activity of the gland is due to the release of iodine la­
beled hormone.

This interpretation is justified by the

findings in vitro (46,47) and also by the fact that almost
all of the organically bound iodine which is delivered to
the blood circulation is thyroxine and triiodothyronine
(48,49).

The decrease in 1-151 in the thyroid may, there­

fore, be considered to reflect secretion of 1-151 labeled
hormone (59).

The conversion of monoiodotyrosine or di-

iodotyrosine 1-151 to thyroxine 1-151 and triiodothyronine
1-151 would not influence the results obtained by external
counting.

One factor that could be of importance is the

loss of inorganic 1-151 from the gland.

This is known to

occur as a result of exchange with 1-127*

it must be

pointed out, however, that 40 hours after the injection of
a tracer dose of radioactive iodine, almost all the thyroid
1-151 is in organic (non-exchangeable) combination (49).

5
The loss of the radioactivity from the thyroid gland
can be based on the per cent output per unit of time or on
its biological half-life which is the time required for
loss of 50 per cent of the radioactivity from the thyroid
gland.

Corrections must be made for the physical decay of

radio-iodine.

This method, however, does not give a quanti­

tative estimation of the thyroid secretion rate, and it is
of value only on a comparative basis.
Perry (51) in 1951 reported that when rats are given
1-131 and different groups are then given graded doses of
thyroxine, inhibition of thyroidal 1-131 output during a
48-hour period is proportional to the dosage of thyroxine
administered.

He proposed this as a thyroid assay method.

Wolff (50) used a technique similar to Perry's in studying
some factors that influence the release of iodine from the
thyroid gland.
Reineke and Singh (52) and Henneman et al. (53) mod­
ified Perry's technique.

They gave graded doses of thyrox­

ine successively to the same individual, after the animals
had previously been treated with 1-131, instead of giving
graded doses of thyroxine to different individuals or dif­
ferent groups.

This technique has the advantage over the

goitrogen method in that the study can be conducted on in­
dividual intact animals.

OBJECTIVES AND EXPERIMENTAL APPROACHES
Little work had been done on inheritance in regard
to the endocrine system and particularly that of the thy­
roid gland.

Mixner and Upp

(38)

found strain differences

in the thyroid secretion rate of several strains of chickens
and Hurst ejb al..

(35)

reported that three strains of mice

showed differences in the thyroid secretion rate.
Several pure inbred strains of mice developed by
brother x sister matings for more than twenty generations
were selected.

These mice were genetically homogeneous

(Heston,

and, therefore, it was safe to suggest that

54),

any differences which might exist in thyroidal activity,
among these strains, would be due to heritable factors,
particular for each strain.
Thyroid 1-131 uptake, output rate constant and thy­
roid hormone secretion rate by the method of 1-131 adminis­
tration and the use of exogenous thyroxine (Perry,
and Reineke and Singh, 52 ) were
roid activity.

51,

used as criteria for thy­

The mice used were A/Jax, BALB/c, C57BR and

C57BL and the hybrids CAF-^ and BBF^.
A large number of heterozygous mice were primarily
used to establish a method for determining the thyroid hor­
mone secretion rate.

7
Materials and Methods
Heterozygous mice, pure inbred strains and their F^
hybrids were used in this study.

Heterozygous mice were

obtained from Carworth Farms and from the Michigan State
Health Laboratory.

Inbred mice of strains A/Jax, BALB/c,

C57BR/cd, C57BL/6 and the F^ hybrids, CAF^(BALB/c# x A/Jax J1)
and BBF1(C57BL/6£

x

C57BR/cd<?) were obtained from the Jack­

son Memorial Laboratory.

The parental strains are well es­

tablished inbred lines maintained by brother-sister matings
for many generations (54-).

The inbred mice within each

strain or their F^ hybrids are theoretically identical in
genetic background.
The animals were fed with Hoppert's ration consisting
of yellow corn meal 14-0 parts, ground whole wheat 100 parts,
alfalfa leaf meal 24- parts, whole milk powder 80 parts,
Brewer's yeast 12 parts and iodized salt 4- parts.

Animals

were kept in an air-conditioned room with a temperature of
approximately 74-°F all through the year.
was maintained from

Constant lighting

8:00 A. M. until 10:00 P. M.

Mice used

were of both sexes,with ages ranging from a few weeks
few months.

to a

Their body weights ranged from 17 to 50 gm.,

varying with age and sex.
Mice were allotted to groups,
ten animals in each

group.

ranging from five to

The micefrom the Carworth

Farms were studied in two or three trials.

In the first

experiment, the 1-131 uptake and output rate constant were

8
determined.

The same mice were again used to establish the

thyroid hormone secretion rate by the method of 1-131 ad­
ministration and the use of exogenous thyroxine.

The time

elapsed between the first and the second experiment on the
same group was at least three weeks.

The mice were given

doses of carrier-free 1-131 ranging from 5 uc to 20 u c , with
an average of 10 uc per mouse.

There was no special reason

for the level of 1-131 given, except that a higher dose was
more appropriate to obtain a higher counting rate.

It was

assumed, however, that this range of 1-131 was below any
toxic dosage of radiation.
The subsequent experiments were somewhat modified,
when it was found that the retreatment of mice with rela­
tively high amounts of 1-131 damaged the epithelial cells
of the thyroid follicles.
Mice from the Michigan State Health Laboratory were
selected.

The amount of 1-131 administered to these groups

did not exceed 1 uc per mouse.

In order to obtain higher

counts, the geometry of the apparatus was changed.
A much thinner lead shield with only 1.2 mm. of
thickness was used, whereas in the earlier experiments a
shield with 4.8 cm thickness was applied.

It was thus pos­

sible to increase the counting efficiency four to five
times and to some extent compensate for the lower level of
I-I3I dose used.

Furthermore, in order to avoid any damage

9
to the thyroid gland, each group of mice was used only
once, unless otherwise stated.

It did not seem probable,

however, that such a low dose would do any harm to the thy­
roid follicles.

On these mice, only 1-131 uptake and thy­

roid hormone secretion, by Perry's method, was determined.
Inbred mice from Jackson Memorial Laboratory were
used to determine the radio-iodine uptake curve, output
rate constant and the thyroid hormone secretion rate.

To

measure the uptake and output curves of each strain, two
mice from each sex of each strain were selected.

Five uc

of carrier-free 1-131 was injected intraperitoneally into
each mouse.

Counts were taken at frequent intervals from

7-180 hours after 1-131 injection, with shorter intervals
at the beginning and longer intervals at the end.

The per­

centage of the injected dose was calculated for each count.
The results are plotted as the log of per cent of injected
dose against time in hours.
To measure 1-151 uptake and thyroid hormone secre­
tion rate the mice were divided into two groups with 12
mice of each strain in each group.

Five uc of 1-131 was

injected as before.
Two counts were taken on each mouse at 48 and 96
hour intervals after 1-131 injection.

Thyroid hormone se­

cretion rate was determined by the method of Reineke and
Singh.

This method requires more days of counting— at

10
least ten days after 1-131 in.jection— and, in order to have
reliable counts, it was not possible to use less than 5 uc
1-131*

In Perry's method only two counts are sufficient,

with four days' interval between them.
Measurement of 1-131 Uptake, Output Rate Constant
and Thyroid Hormone Secretion Rate
I.

1-131 Uptake:

Either 24- or 48 hours after ra-

diodiodine injection, external thyroid counts were obtained.
1-131 uptake was calculated on the basis of the per cent of
the injected dose detected in the thyroid gland.
II.

Measurement of the Output Rate Constant:

cient time was given, after 1-131 injection, for the thy­
roid gland to take up the radioiodine and to let the excess
iodide be excreted.
were obtained.

After 24 or 48 hours uptake, counts

The log of the per cent of injected dose

was then calculated and plotted against time in days.
straight line was fitted to the points.

A

The slope of the

line gives the exponential rate of loss of 1-131 from the
thyroid gland, which can be expressed either as the per
cent output per day or the biological half life.

This ex­

ponential loss of 1-131 can be expressed with the equation:
A,
-nj
= e
where A. and A are the activities at time t
A
’
t
o
o
and at zero time sugsequently, and -B is the turnover rate
constant of 1-131-

Suffi­

11
III.

Determination of the Thyroid Hormone Secretion

Rate by Injection of 1-151 and Exogenous Thyroxine:
a.

Perry's Method:

Seven groups of ten mice each

were given 0.4 uc 1-131 per mouse.

Each group except the

controls received graded doses of 1-thyroxine twenty-four
hours after injection of 1-131.
was continued for four days.
on the fifth day.

The thyroxine treatment

A second count was then taken

Each mouse was counted at the same time

of the day in both counts, so that the time between the
first and second counts was approximately the same for all
the mice.

The counts were corrected back to zero time and

the per cent of the initial count was calculated for each
group.

The per cent of previous count was plotted against

the thyroxine dosage in ug. per hundred grams of body
weight on coordinate paper.

A regression line was fitted

to the ascending portion of the curve by the method of
least squares with the prediction equation

Y = a + bX.

If

the per cent of previous count (Y) is taken as 100 or 1.00
(Figures 2-21, Appendix), the thyroid secretion rate (X) is
then estimated as ug/100 gm. body weight.

In some cases

the per cent of previous count leveled off before it reached
100 per cent (Figure 4, Appendix).

In such cases the (Y)

was determined at the point where the line leveled off.
b.

Measurement of Thyroid Hormone Secretion date by

Method of Reineke and Singh:

This technique is a modifies-

12
tion of Perry's technique, the thyroxine dose being pro­
gressively increased on the same group of mice.

This method

allows one to observe the degree of I-l^l output inhibition
by various amounts of thyroxine on each individual mouse.
This method, however, takes a longer time and requires at
least three to four counts on the ascending portion of the
curve in order to obtain reliable values.
Counting Method:

A Scintillation Counter* was used.

External thyroid counts were taken by use of a heavy lead
counting table similar to that described by Albert (55)*
The voltage used was 1100.

The count rate meter was always

calibrated before counting was done.
was used to check the machine.

A cobalt-60 standard

The mice were restrained in

a long taper conical 50 nil. centrifuge tube with a nose
opening at the end.

The thyroid region was centered over

the tapered opening in the counting setup.

The length of

time required for counting each mouse varied between 5 and
5 minutes, depending on the activity of the gland.

With a

high count, the count rate meter quickly adjusted to a
stable reading, whereas with low counts it was necessary to
wait for a few minutes before a reliable count could be re­
corded.

The sensitivity was always set at the 10 second

time interval.

♦Nuclear Instrument and Chemical Corporation, Model
DS-1.

13
Preparation of Standard:
time of radio-iodine injection.

Standards were made at the
Ten per cent of the inject­

ed dose was usually put within a 5 nun. circle drawn in the
center of a small porcelain dish with a wax pencil.

The

standards were left for a few hours in order to dry and
then counted.
standard.

This count was considered the zero time

It was found that the loss of counts of the

standards on the days subsequent to their preparation were
higher than the loss which could be accounted for by phys­
ical decay, even when they were prepared in casein.

This

loss was exponential, with a half life of approximately six
days, as shown in Pig. 1 of the Appendix.

In order to

avoid systematic errors, all the calculations which re­
quired the use of a standard were referred back to the ac­
tivity of the standard at zero time.

Standards were used

only to obtain the uptake values.
Body background was taken over the epigastric region.
The thyroid counts were corrected by one-half the body
background plus the general background as suggested by
Wolff (50).

This method of measuring the background could

have given too high values because of the collection and v
excretion of the radioiodine from the bladder.

It was safe

to assume- that all the extra radioiodine which was not col­
lected by the thyroid gland had already been excreted
through the urine by the time the 48 hour count was taken.

14
For the measurement of the radioiodine uptake curves of the
inbred mice, where counts were taken every few hours after
1-131 injection, Wolff*s correction for the body-background
did not seem adequate, since considerable amounts of radio­
iodine were still present in the extrathyroidal tissues and
particularly in kidney and bladder.

Since we were primari­

ly interested in results on a comparative basis, possible
errors in calculating the per cent of injected dose and also
in correcting the background did not affect the results to
an appreciable extent.
Preparation of Thyroxine Solutions:

The L-thyroxine

used was supplied by Glaxo Laboratories, Greenford, Middle­
sex, England.

L-thyroxine crystals were purified by Dr.

E. P. Reineke and kept in a desiccator in the refrigerator.
Ten mg of crystallized thyroxine was weighed on an analyti­
cal balance, dissolved in distilled water in a 50 cc. beak­
er and made slightly alkaline with NaOH.

Enough acid (HC1)

was added to make the solution slightly cloudy; at this
point the monosodium salt of thyroxine is formed.

This

solution was then placed in a 100 cc. volumetric flask and
distilled water was added up to the mark.

This solution

contained a concentration 100 ug. of l-thyroxine per ml. of
solution.

The stock solution was stored in the refrigerator.

RESULTS
Heterozygous Mice
Radioiodine Uptake Values
Groups of mice, each group consisting of ten indi­
viduals, were used.

The amount of carrier-free 1-131 given

was between 10 and 20 uc per mouse and is indicated in ap­
propriate tables (Tables I-VI, Appendix).

The averages of

48-hour radioiodine uptake with their standard errors are
summarized in Table I.

The 48-hour uptake for each indi­

vidual mouse of each group appears in Appendix (Tables IVI).

Table II shows the averages for the 24-hour uptake

values for the mice from the Michigan State Health Labora­
tory.

Forty-eight-hour uptake was not measured in the mice

from the Michigan State Health Laboratory, because the mice
were treated with thyroxine 24 hours after the 1-131 injec­
tion for the measurement of thyroid secretion rate by
Pe r r y ’s method.

The averages of the 48-hour uptake values

are between 5 and 11 per cent of the injected dose, as
shown in Table I.

The results obtained for the 48-hour up­

take on mice from Carworth Farms in the second experiment
did not substantiate the observations of the first experi­
ment which showed a slightly higher 48-hour uptake for the
males.

16

TABLE I
AVERAGE PER CENT 48-HOUR UPTAKE AND THEIR STANDARD
ERRORS IN MICE FROM CARWORTH FARMS
Average
Sex

Trial No.

9
9
9

$
A
o

$

%

48-Hour Uptake

First
Experiment

Second
Experiment

1

7.77*1.27

11.30*1.28

2

6.11±0.40

7-23*0.70

3

5-08±0.36

9.96+1.26

4

8.39*0.93

7.67*0.70

5-

10.64±2.00

8.90±0.77

6

8.45±1.10

6.90+0.28

♦Values obtained for each individual mouse and the
number of mice in each group appear in the Appendix.

17

TABLE II
2A— HOUR AND 48-HOUR' UPTAKE OF MICE FROM MICHIGAN
STATE HEALTH LABORATORY*
First
Experiment
1/17/56
Group
No.

Second
Experiment
2/1/56

Third
Experiment
3/9/56

•
No. of
mice
in each
group

Average
24 hrs.
uptake

No. of
mice
in each
group

Average
24 hrs.
uptake

No. of
mice
in each
group

Average
48 hrs.
uptake

1

10

15.40

10

13.84

10

16.10

2

10

13.60

9

13.08

10

19.90

3

9

12.66

10

10.86

10

14.44

4

10

12.89

10

11.00

10

17.90

5

10

14.12

10

12.30

10

13.40

6

10

11.10

10

11.40

10

15.54

Average
*The mice in the Second Experiment are the same mice
as those used in the First Experiment.
Both times they re­
ceived .4 uc 1-131.
Mice of the Third Experiment received
1.0 uc 1-131.
The mice were approximately 5 weeks old at
the time of the First Experiment.

18
The mice from Michigan State Health Laboratory
seemed to have a higher uptake than the mice from Garworth
Farms.

Unfortunately, the comparison cannot be made be­

tween these mice and those from Garworth Farms, because of
the differences in time v/hen uptakes are measured and also
because of the wide differences in the radioiodine dosage.
A frequency distribution of 48-hour 1-131 uptake for
the mice from Garworth Farms, regardless of sex, is also
presented (Figure 1).

It is noted that almost 50 per cent

of the uptake values fall within 4 to 6 per cent of the in­
jected dose.

In more than 80 per cent of these uptake val­

ues, the range is between 3 and 7 par cent of the injected
dose.

The uptake exceeded 7 par cent of the injected dose

in only 20 per cent of the uptake values.
Determination of Per Gent Output per Day and
Biological Half-Life (T)&)
These two express the output rate or turn-over rate
of the thyroid hormone.

Per cent output per day and bio­

logical half-life (TJ£) were calculated.

The averages of

the per cent output per day and the standard errors appear
in Table II.

The values obtained for per cent output per

day and also the biological half-life for each individual
mouse of each group is observed in Appendix Tables I to VI.
The average per cent output per day were as follows:
male mice:

fe­

13.72*1.08; 17.00±1.1; 7.10*0.44 for the first

20
run, and 18.02*1•46; 14.00*1.62 and 18.89*0.83 for the sec­
ond run, and for males:

13.12*1.12; 14.10*1.10; 14.80*0.83

for the first run, and 12.67±1.50; 19.42+3.40 and 16.10*
1.70 for the second run.

There do not seem to be any sig­

nificant differences between males and females.

A low value

of 7*1 per cent per day for the females of trial 3 on the
first run cannot be explained.

This low value is apparent­

ly due to experimental error, since on the second run an av­
erage value of approximately 19 per cent per day was ob­
tained.

The results for per cent output per day were not

consistent in regard to sex differences.

Moreover, the

output rate values were relatively close for both the first
and the second experiment, as is seen from Table III.

This

might suggest that the effect of radiation which damaged
some of the thyroid follicles, as the histological studies
showed, did not affect thyroid function appreciably.
A frequency distribution of T/fe is also given for
both sexes of mice from Garworth Farms (Figure 2).

These

include the values of the first and the second experiment.
Seventy-three per cent of the T# values were within 3-6
days, with a majority distributing within 4 to 6 days.
An attempt was made to find whether there was any
correlation between the per cent uptake and output rate
constant in the heterozygous mice.

Forty-eight-hour uptake

was plotted against the biological half-life for every

21

TABLE III
AVERAGE PER CENT OUTPUT PER DAY AND THEIR STANDARD
ERRORS IN MICE* FROM CARWORTH FARMS
Average % Output per Day
Sex

Trial No.

9

First
Experiment

Second
Experiment

1

13.72±1.08

18.02*1.46

9

2

17.0 ±1.1

14.0 ±1.62

9

3

7.1 ±0.44

18.89±1.23

6

4

13*12±1.12

12.67±1.50

3

14.10+1.10

19.42+3.40

6

14.80*0.83

16.10±1.70

$
&

♦Values obtained for each individual mouse and the
number of mice in each group appear in the Appendix.

23
mouse of each sex.

There was no significant correlation

between these two values (Figure 3)-

There was a trend,

however, towards a longer T}6 with a lower uptake.

The non-

linearity between these two values was indicated by the ab­
sence of any correlation.
Measurement of Thyroid Secretion Rate of
Heterozygous Mice
The method of Reineke and Singh and that of Perry
were used to measure the thyroid secretion rate.

Figures 4

to 11 of the Appendix show the extrapolated results for the
thyroid secretion rate of these mice.

The equation of the

line, standard errors of the mean and the correlation rxy
between Y, the per cent of previous activity, and X the
thyroid secretion rate are indicated in appropriate figures.
The correlations between X and Y were all highly signifi­
cant.

The values of X measured by Perry's method are as

follows:
weight.

3.08, 2.26, 2.09 and 2.26 ug./lOO gm. body
The values of secretion rate measured by the meth­

od of Reineke and Singh are l.?6, 1.31* 1.26, 2.18 and 3*09
ug.

These mice were obtained from Garworth Farms, whereas

the mice used to measure thyroid secretion rate by the
method of Perry were provided from Michigan State Health
Laboratory.

23
Mice of Inbred Strains and Their F-^ Hybrids
Radioiodine Uptake
Tables IV and V show the radioiodine uptake in dif­
ferent strains of mice 7-180 after 1-131 injection, and the
average percentage of 48-hour uptake. Tables VII-IX of the
Appendix show the results of analysis of variance of strain
differences.

The values show that C37BL/6 and their BBF^

hybrid had values consistently lower than albinos of A/Jax
and BALB/c strains and their CAF-^ hybrid.

Figure 4 shows

the comparative values for the 48-hour uptake.
Measurement of Output Rate Constant
Table V and Figures 4 and 3 show the results ob­
tained.
The uptake of 1-131 a few hours after 1-131 injec­
tion was very irregular but was stabilized after 24 hours.
This might have been due to incomplete 1-131 uptake by the
thyroid gland and that the excess of 1-131 had not yet been
excreted.

The body background

at early hours was very

high and in some cases even higher than the thyroid counts.
It was shown that the thyroid was still taking up iodine 21
hours after I—131 injection.

It was observed that the

C37BL/6 strain had the highest output rate.
were second and C37BR/cd third in order.

The BBF^ mice

From the analysis

26
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28

n

% 1-131

Up-take

^

$ 1-131

Turn- over

I
*-

$ 1-131 UP-TAKE

20

- 30

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C57BR/cd

BB f T

C57BL/6

Average percentage of I— 131 uptake and rate of turn—over
In six genetically different strains of mice

LOG

PERCENTAGE

UPTAKE

29

72

96

x?o

rfcr

5

HOURS AFTER 1-131 INJECTION.
Fig,

5* Log percentage of 1-131 uptake with respect to
time following injection in mice from four
different inhred strains

30

of variance it; was found that both variances attributed to
genotype and genotype x sex were highly significant (Tables
VII and VIII of Appendix).

The level of significance at

^•05 kstween any two group means was obtained as 4,02 per
cent.

The differences between the means for C57BL and that

for any other group except BBF^ were significant.

No sig­

nificant difference between the means for A/Jax and BALB/c
was shown, but the difference between that of CAF-^ mice and
their maternal parent, A/Jax, was significant.
Measurement of Thyroid Secretion date in Inbred Mice
and Their
Hybrid
The method used was that of Reineke and Singh.

The

results are plotted as the per cent of previous activity,
against the thyroid secretion rate in ug/103 gm. of body
weight.

The equation of the line, correlation between X

and X and the standard errors of the means appear in the
Figures 10-21 of the Appendix.

#hen Y, the fraction of

previous activity, is equal to 1.00, X is the thyroid se­
cretion rate.
In order to be able to test for differences in the
thyroid secretion rate among different strains, the thyroid
secretion rate of each mouse of each strain was measured
and treated by the method of least squares.

The values ob­

tained for each mouse and the average in each strain are
seen in Table VI-

31
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o
•
OJ

CO
oo
•
r—I

i—l
LA
•
Ol

KN
UN
♦
rH

i—1

A
NO
•
rH

o•
Ol

+ ID
4 O
0 0 rH
a

a

X
CD

Ph

d
IQ

I—1

CD

VD*

<D
w

o

a

•

OJ

rH

m

rH

KN
00
•
OJ

00
KN
•
OJ

OJ
A
*
OJ

4
NO
•
1-- 1

4
KN
•
rH

00
4
•
rH

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«

LA

4
00
•
OJ

NO
ON
•
rH

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•
rH

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•
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LA
•
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A
A

+1 UN
4 O
0 0 rH

•
rH

rH

HH L A
UN 00
K N rH

<4

o

•
OJ

a

a

a

KN

4

lA

vD

IN

CO

<4

O

r -t

r— I

rH

OJ

CD
P
cd

d

a

d

o
•H

POO
K N rH
rH i—1
OJ

CO
•H

rH

a

p
CD
d
O
cd

•
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d
cd

D 2
* cd

CD

CO

u<d

P

>

CD

ho
cd

C\j

a

0
e

CD
cd

The values obtained are as follows for males and fe­
males of each strain:

A/Jax 2.13*0.118 and 1.84*0.108;

BALB/c 2.44*0.210 and 1.93*0.118; C57BR/cd 3.35*0.345 and
2.45*0.108; C57BL/6 4.19*0.643 and
body weight.

3 * 33*0.341 ug/100 gm. of

The secretion rate for the hybrids CAF^ and

BBF^ males and females, respectively, were:

2 .34*0 .185;

1.84*0.106 and 3-79*0.644 and 2.74*0.268 ug./lOO gm.

Fig­

ure 6 is a graphical representation of the thyroid secretion
rate in each sex of each strain.

The order of magnitude in

the secretion rate of different strains of mice and their
Fx hybrids were C57BL/6, BEF1 , C57BR/cd, BALB/c, CAF1 and
A/Jax.

Analysis of variance showed (Table IX of Appendix)

a significant difference between the different strains of
mice as follows:

C57BL had a significantly higher secre­

tion rate than all other strains, except BBF-^.

BBF^ was

significantly higher than all other strains except C57BL.
C57BR/cd had a significantly higher secretion rate than the
strains A/Jax, BALB/c and the hybrid CAF^

There was no

significant difference in the thyroid secretion rate among
strains A/Jax, BALB/c and their CAF-^ hybrid.
When all the data on each sex of each strain were
plotted and treated by the method of least squares, slight­
ly different values from that when the values of each was
treated separately were obtained.
pendix represent the results.

Figures 10—21 of the Ap­

The values of the secretion

33

L-THY30XINE

U

3

9 2

1

Fig .6*

Thyroid secretion rate of inbred and the
hybrid
mice. The secretion rate is expressed as ug./lOO
gm. of "body weight. The striped bars represent the
standard error of each sex of each strain.

rate for males and females of each strain and their F^ hy­
brids are as follows:

A/Jax, 2.09 and 1.77; C A F ^

2.56 and

1.67; BALB/c, 2.07 and 1.65; C57BR/cd, 5.67 and 3.04; BBF^,
3*97 and 2.85; C57BL, 3*37 and 3*04.

Highly significant

correlation was observed between the X and Y values as fol­
lows:

0.818, 0.845, 0.732, 0.758, 0.938, 0.783, 0.900,

0.786, 0.822, 0.862 and 0.814 for the males and females of
A/Jax, CAF^, BALB/c, C57BR/cd, BBF^ and C57BL/6, respec­
tively.
It is of interest to note that males had a consist­
ently higher secretion rate than females, although the sta­
tistical analysis did not show the differences to be sig­
nificant, except in the C57BR strain, when the data were
treated for individual mice.

The values obtained for the

CAF^ and BBF^ hybrids were intermediate between their par­
ent strains.

DISCUSSION
The results obtained from the heterozygous mice are
influenced by a few variable factors, such as the 1-131
dose range, age, season and their source.

These heterozy­

gous mice, however, showed some uniformity in their 48-hour
uptake and their output rate constant (Tables I and II).
The 1-131 dose range did not seem to affect the iodine up­
take.

Although 1-131 injection damaged the thyroid gland

of the mice from Garworth Farms, when they were treated
with 1-131 for the second or third time, the 1-131 uptake
still remained approximately the same, nor did the output
rate constant change to any appreciable extent.

The pos­

sible explanation is that the undamaged follicles of the
thyroid had a compensatory increase in action, and the thy­
roid was still apparently able to function normally.

In

one case when 100 uc 1-131 was injected into a group of
mice, a very rapid release of the 1-131 from the thyroid
indicated the complete disruption of the thyroid follicles.
The thyroid secretion rate, measured both by the
method of Reineke and Singh and the method of Perry, gave
values between approximately 1.00 and 3*00 ug./lOO gm. body
weight.

It is not possible to draw any conclusion about

the wide difference in the thyroid secretion rate.

It

might be due to the way the 1—thyroxine solutions were pre­
pared.

The high values obtained might have been due to

racemization of 1—thyroxine, which reduces the thyroxine
activity considerably (56,57)*

In the case where the thy­

roid secretion rate of mice was found to be 3*00 ug. (Figure
3 of Appendix), which seemed to be too high, the melting
point of the thyroxine solution used was measured, as a
test for racemization.
tained.

No definite answer could be ob­

The small amount of the crystallized thyroxine did

not allow measurement of the optical rotation as a test for
1-thyroxine.

The fact that these mice were run at differ­

ent times of the year might have contributed considerably
to these differences in the thyroid secretion rate.
These sources of error, namely, dosage range, thy­
roxine preparations, age and season, were eliminated for
the inbred and their F^ hybrid mice.

The same stock solu­

tion of thyroxine was used for all these mice.

The mice

were all approximately at the same age at the time of ex­
periment.

The 1-131 dosage was constant, 5 uc per mouse.

The results obtained on the inbred mice are inter­
esting in that significant differences among different
strains are observed.

C57BL had the highest output rate

constant, as measured by the per cent of I—131 loss per
day, and the highest thyroid secretion rate.

The values on

BBF1 hybrid, both in output rate constant and thyroid secretion rate were intermediate between its parent strains.

37
The CAF^ hybrid had values for thyroid secretion rate in­
termediate between its parent strains, but showed a higher
uptake and lower output rate than its parent strains.
Female mice had in general a higher output rate con­
stant.

This was not consistent for all the strains.

The

values obtained for thyroid secretion showed a higher rate
for males than for females, which was consistent for all
the strains.

Since both the output rate constant and meas­

urement of thyroid secretion rate are actually an expres­
sion of the same factor, namely, release of organically
bound iodine, their difference in the same mice may be due
to possible experimental error rather than actual differ­
ences.

These differences, however, were statistically in­

significant and cannot be taken as conclusive evidence.
A reciprocal relationship exists between the 1-131
uptake on one hand and the output rate constant and thyroid
secretion rate on the other hand which was explained pre­
viously.

A low uptake in strain C57BL, which has the high­

est secretion rate, might prove that a high per cent uptake
of 1-131 does not indicate a high thyroidal activity by it­
self.

It is interesting to note that these strains of mice

and their

hybrids show different behaviour as far as the

thyroidal activity is concerned.

These finding are in

agreement with other experiments of a completely different
nature, which appears in the following.

38
The C57 strain is probably the most widely used in
various fields of biological research.

Some of their bio­

logical properties have been found quite distinct from
those of other strains.

For instance, it has been shown

that the C57BL mice are more aggressive in competition for
food than the BALB/c, highly resistant to cold, superior to
BALB/c in fighting (58), and more vigorous and rugged by
observation than most other inbred mice.

The present find­

ings agree quite well with these traits in that the thyroid
activity of the C57BL is the highest among those which we
studied.
Histological studies have shown (59) that the fol­
licles of the thyroid gland of the C57 strain have a larger
cell height than G^H strain which is similar to the A/Jax
and BALB/c strains.
In connection with cancer research, C57BL mice are
in general less susceptible to different types of tumors,
except sarcomas, but evidence indicates that these mice are
highly susceptible to pituitary tumors after thyroidectomy
(60,61).

It was also found that all pituitary tumors which

were assayed were thyrotropic and of the dependent type
(62).
From the genetic standpoint the differences between
the means of the F-^ hybrids and that of their respective
parents, with the exception of CAF^, which showed different

39
values, in both iodine uptake and output rate constant are
of interest.

The

hybrids have radioiodine uptake and

thyroid secretion rate values intermediate between their
parent strains.

Although these animals are not

signif­

icantly different from their parents, they may indicate
that thyroidal iodine uptake and its output rate are two
genetically separate phases of thyroid function and that the
intermediate values for uptake and output rate constant are
a result of hybridization, which requires multiple factors
with dominant genes.

The hypothesis suggested from the re­

sults of uptake and output rate constant along with the
thyroid secretion rate is that both thyroid iodine space
and the release of the hormone from the thyroid gland are
controlled by separate genetic factors.
Although our results are not exactly in agreement
with the findings of Mixner and Upp (38), wdo found a much
higher thyroidal activity in hybrid chicks, as compared to
single cross chicks, they both suggest a genetic transmis­
sion of thyroidal activity.

In the experiments reported in

this paper, the thyroid activity of the hybrid mice did not
exceed both paternal and maternal parents, but was inter­
mediate between them.

This does not exclude, however, the

possibility of heterosis, suggested by Mixner and Upp.
Strain differences have been observed in the thyroid
uptake of the strains A, C57 &n<I I ^7

Lyor (63)*

Uyon

40
measured the thyroid uptake of these strains of mice at in­
tervals from 2 to 48 hours after radioactive sodium iodide.
He found a 1)£ to 2 times higher uptake in A mice than the I
strain*

The values for the C57 were found to be between

those of the other two strains.
Although the higher thyroid uptake alone does not
indicate a higher thyroidal activity, it does suggest, how­
ever, a strain specificity.

L^yon, furthermore, found that

after the administration of one IU of TSH, one hour before
the iodide injection, the increase in 1-151 uptake was four
times greater in the A strain than in the 057 mice.
Aside from the genetical differences in thyroid ac­
tivity, numerous studies have been conducted on physiologi­
cal and biochemical aspects which indicate strain speci­
ficity (64,65,66,67)-

special interest are the findings

of strain differences in mice and rats given alloxan (68).
Based on the studies on alloxan-treated mice and rats,
Beach et al.(68) suggested the existence of radically dif­
ferent endocrine endowment in different strains.
Further investigations are required to draw definite
conclusions as to the heritable factors involved in the
thyroid and other endocrine systems.

SUMMARY AND CONCLUSIONS
Inheritance of thyroid activity was investigated.
Pure inbred mice and their

hybrid were used.

These mice

were A/Jax, BALB/c, C57BR/cd, C57BL/c ani their F^ hybrid,
CAF1 (BALB/c^ x A/Jax 3*) and BBF1(C57BL/6^ x

C57BR/cd£).

The mice were obtained from the Jackson Memorial Laboratory.
These mice were produced by brother x sister matings for
more than 20 generations and are, therefore, considered to
be quite homogeneous.
I-lJl uptake and its turn-over rate was measured.
Turn-over rate was detected by:

1) the measurement of the

exponential rate of release of injected radioiodine from
the thyroid gland of the intact animals, and 2) by the
method of 1-131 injection and the use of exogenous thyrox­
ine which was required to inhibit the release of radioiodine
from the thyroid gland.

Heterozygous mice which were ob­

tained from the Carworth Farms and from the Michigan State
Health Laboratory were primarily used to establish a method
for the thyroid secretion rate.
The thyroid secretion rate was measured by the ad­
ministration of graded doses of 1—thyroxine either into
different groups (Perry* s method) of mice, or to the same
individual mouse (Reineke and Singh).

The amount of 1—

42

thyroxine which was required to prevent the output of ra­
dioiodine was considered to be equal to the amount of thy­
roid hormone which is normally put out by the thyroid gland
of the animal itself.
The results indicate that the strains A/Jax, BALB/c
and their CAF-^ hybrid had a high 48-hour uptake and low
"turn-over rate/' whereas the strains C57BL/6, C5?BR/cd and
their BBF^ hybrid showed a low 48-hour uptake and a high
turn-over rate.

C57BL/6 had the highest turn-over rate and

the lowest uptake.
Statistical analysis showed that the C57BL strain
was significantly different from all other strains studied
except BBF^.

C57BR was also significantly different from

the strains A/Jax, BALB/c and their CAF^ hybrid.

There

were no significant differences among the strains A/Jax,
BALB/c and the CAF^ hybrid.
A reciprocal relationship was observed between the
48-hour 1-131 uptake and its turn-over rate in the inbred
mice and their F-j^ hybrids, but not in the heterozygous
mice.

The values obtained for the thyroid secretion rate

on^the inbred mice and their F1 hybrids show values for the
CAF^ and BBF^ in both cases intermediate between their par­
ent strains.
The results support the view that the thyroid mecha­
nism is under genetic control.

Furthermore, it appears that

43
thyroidal iodine "space," as indicated by the uptake data,
and the mechanism controlling thyroid output are regulated
by separate genetic factors.

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45

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Silberberg, R., and M. Silberberg. 1954. Skeletal
Effects of Radio-Iodine Induced Thyroid Deficien­
cy in Mice as Influenced by Sex, Age and Strain.
Amer. J. Anat. 95:263-282.

66 .

McLaron, A., and D. Michie. 1954. Are Inbred Strains
Suitable for Bio-Assay? Anim. Breed. Absts. 22:
353.

67.

Young, G. B. 1953. A Study of Genotype-Environment
Interaction in Mice. J. Agric. Sci. 43:218.

68.

Beach, E. F., J. B. Phoebe, J. Bradshaw, and 0. S.
Cullimore. 19 . Alloxan Reaction in Albino
Rats as Affected by Strains Differences. Fed.
Proc. 14:179*

1956.

(Personal Communications)

1956. Carcinogenesis by
Cancer Research 16:5-20.

APPENDIX

52
TABLE I.

TRIAL 1

THE VALUES OBTAINED FOR THE PER GENT OF INJECTED DOSE,
THE PER CENT OUTPUT PER DAY AND THE BIOLOGICAL
HALF-LIFE FOR EACH INDIVIDUAL i.OUSS OF THE
CARtfORTH STRAIN

Mouse
No.

First Experiment *
3/21/55

Second Experiment *
7/1/55

Injected with 10 uc 1-131

% Uptake
at
48 hrs.

% Output
per Day

T% in
Days

Injected with 20 uc I--131
% Uptake
at
48 hrs.

% Output
per Days

T% in
Days

1

11.45

12.00

5*75

5.62

21.70

3*19

2

5*69

13*26

5*22

16.78

21.30

3*25

5

5*52

16.00

4.31

-

-

4

4.74

13*44

5*15

8.01

16.50

4.20

5

16.13

14.43

4.80

14.98

22.90

2.67

6

8.48

8.61

8.48

13*04

10.30

6.72

7

7*59

13*10

3*29

11.23

15*80

4.39

-

-

8

-

-

-

-

-

9

5*52

17*80

3*89

11.20

19*70

3*51

10

5.06

14.90

4.65

9*55

16.00

4.33

11.30±1.28

18.02±1,46

Average 7*77±1*27

13* 72±1.08

*The same mica war© used in Loth, the First and the Second
Experiment.

53
TABLE II.

TRIAL 2

THE VALUES OBTAINED FOR THE PER CENT OF INJECTED DOSE, THE
PER CENT OUTPUT PER DAY AND THE BIOLOGICAL HALF-LIFE
FOR EACH INDIVIDUAL MOUSE (CARWORTH)

Mouse
No.

First Experiment *
3/21/55

Second Experiment *
7/15/55

Injected with 10 uc 1-151

Injected with 15 uc 1-151

% Uptake
at
48 hrs.

% Output
per day

T1A in % Uptake
at
days

% Output

48 hrs.

per day

T}£ in
days

11

5.12

13-90

4.98

9.36

9.70

7.14

12

6.21

17.60

3.93

6.85

19.80

3.50

13

5.36

10.00

6.93

7.71

8.10

8.55

14

5.85

21.40

3.25

15

6.45

17.80

3-89

16

6.79

20.50

5.41

17

5.08

17*90

3.87

18

-

-

-

-

8.48
-

4.15
-

-

15 •60
-

15.40
-

-

4.44
-

4.50
-

19

4.74

17.70

3.91^

7.83

15.50

4.47

20

6.71

16.60

4.17

6.40

13.90

4.98

6.11±.40

17-0±1.1

7.25±.70

14.0±1.62

♦The same mice were used in the First and the Second
Experiment.

54
TABLE III.

TRIAL 5

THE VALUES OBTAINED FOR THE PER GENT OP INJECTED DOSE, THE
PER GENT OUTPUT PER DAY AND THE BIOLOGICAL HALF-LIFE
FOR EACH INDIVIDUAL MOUSE (CARWCRTH)

First Exoeriment ♦
5/5/55

Second Experiment *
7/1/55

Mouse Injected
with 10 uc 1-151
No.
% Uptake % Output T}£ in
at
per day
days
4-8 hrs.

Injected with 15 uc 1-151

% Uptake
at
48 hrs.

% Output
per day

T# in
days

21

5.79

5.90

11.47

10.26

17.50

5.96

22

5.85

8.90

7.78

8.02

18.18

5.68

25

5.55

7.60

9.11

7-57

19.00

5.64

24

4-.89

7.10

9.76

10.17

-

-

25

5.4-0

5.60

12.57

7.57

17.50

5.96

-

-

-

-

-

26

-

27

4-.10

4.90

14-. 14

12.54

18.20

5.80

28

5.92

7.50

9.74

9.47

14.10

4.91

29

5*92

8.10

8.55

8.55

20.70

5.34

50

4-.55

8.50

8.54

15-95

25.90

2.67

9.96±1.26

18.89±1.25

5.08±.56

7» 1±.44-

*The same mice were used in both the: First and the
Second Experiment.

55
TABLE IV.

TRIAL 4

THE VALUES OBTAINED FOR THE PER CENT OF INJECTED DOSS, THE
PER CENT OUTPUT PER DAY AND THE BIOLOGICAL HALF-LIFE
FOR EACH INDIVIDUAL MOUSE (CARWORTH)

Mouse
No.

First Experiment ♦
5/12/55

Second Experiment;*
8/8/55

Injected with 10 uc 1-131

Injected with 15 uc 1-131

% Uptake
at
48 hrs.

% Output
per day-

Tfc in
days

% Uptake
at
48 hrs.

% Output
per day

T>& in
days

1

15.01

13.00

5.33

10.78

11.70

5.92

2

9.34-

17.90

3.84

4.80

19.60

3-53

5

4.61

8.60

8.05

6.45

8.50

8.15

4

7-58

9.00

7.70

8.04

8.10

8.55

5

6.55

13.30

5.21

6

7*53

11.80

5.87

8.04

12.50

5.54

7

5.40

12.90

5.38

8.04

12.50

5-54

8

9.66

13.10

5.29

7.58

15.80

12.65

9

12.05

18.50

3-74

-

-

-

-

-

-

—

—

7.67*.70

12.67*1.5

10

8.39**95

13.12*1.12

-

-

-

-

♦The same mice were used in both the First and the
Second Experiment.

56
TABLE V.

TRIAL 5

THE VALUES OBTAINED FOR THE PER CENT OF INJECTED DOSE, THE
PER CENT OUTPUT PER DAY AND THE BIOLOGICAL HALF-LIFE
FOR EACH INDIVIDUAL MOUSE (CARWORTH)

Mouse
No.

Second Experiment *
8/8/55

First Experiment*
5/12/35
Injected with 10 uc I- 131

% Uptake
at 48 hrs.

% Output
per day

T# in
days

Injected with 13 uc I-131

% Uptake

% Output

at 48 hrs.

per day

T3£ in
days

11

16.16

13.70

5.03

6.86

17.60

3.93

12

6.86

14.60

4.74

7.36

18.80

3.68

15

5-56

17.60

3.93

7.73

41.20

1.68

14

15-72

8.40

8.23

11.42

8.10

8.43

15

12.80

18.80

3.80

7.72

19.00

3.64

16

4.80

13.60

4.44

7.72

18.00

3.80

17

8.28

13.10

4.83

9.42

12.70

5.43

18

-

-

-

-

-

19

21.23

14.40

4.81

12.88

20.00

3.46

20

6.35

8.70

7.96

-

-

-

10,.64±2.00

14.10±1.10

8.90±.77

-

19.42+3.40

*The same mice were used in both the First and the Sec­
ond Experiment.

57
TABLE VI.

TRIAL 6

THE VALUES OBTAINED FOR THE PER CENT OF THE INJECTED DOSE,
THE PER CENT OUTPUT PER DAY AND THE BIOLOGICAL HALF-LIFE
FOR EACH INDIVIDUAL MOUSE (CARWORTH)

First Experiment*
i
5/23/55
Mouse
No.

Second Experiment*
7/25/55

Injected with 10 uc 1-131

% Uptake
at
48 hrs.

% Output
per day

T}& in
days

Injected with 15 uc 1-131
% Uptake
at
48 hrs.

% Output

T1A in

per day

days

21

5.60

12.70

5.45

7.30

17.20

4.02

22

7.75

14.40

4.81

7.00

9.40

7.57

23

4.82

14.30

4.84

6.47

13.00

5.55

24

6.10

11.80

5.87

-

-

-

25

6.03

15.00

4.62

-

-

-

26

5-56

15.10

4.58

6.08

12.90

5.57

27

9.90

13.90

4.98

6.63

14.50

4.77

28

15*62

22.10

3.00

8.80

26.70

2.59

29

9.50

14.80

4.68

6.56

17.60

5.93

50

13.84

14.50

4.77

6.47

17.60

3.93

8•45±1•10

14.80±.83

6.90±.28

16.10±1.70

*The same mice were used in "both the First and the
Second Experiment.

58
TABLE YII

RESULTS OF ANALYSIS OF VARIANCE OF 1-131 UPTAKE
AMONG GENETICALLY DIFFERENT GROUPS OF MICE
AT 48 HOURS AFTER INJECTION
Source of
Variance
Total

Degree of
Freedom

Mean Squares

F

119

Genotypes

5

154-7.05

39.69

Sex

1

77.28

1.98

Genotype x Sex

5

1576.35

40.45

108

38.97

Error
P <^.01

Level of significance between means of two groups at
t .05 and 38 degrees of freedom - 2.60. It was computed as
follows (Snedecor, 1946):
= 1.28

n - 20, the number of individuals in each group
- 16.43, the variance with­
in each group; here the mean
square in the error term was
used.

%
„ „
(nu -m0) - 0
P .03(38 degrees of freedom) * 2.03 *
1 A ____
m l~m2
ml“m2 = 2 *598 -2.60

59

TABLE VIII
RESULTS OF ANALYSIS OF VARIANCE OF 1-131 OUTPUT RATE
CONSTANT AMONG GENETICALLY DIFFERENT
GROUPS OF MICE
Source of
Variance
Total

Degree of
Freedom

Mean Squares

F

119
5

429.64

26.15

Sex

1

28.72

1.74

Genotype x sex

5

460.62

108

16.43

0•
00

Error

OJ

Genotype

Level of significance between means of two groups at
P .05 and 38 degrees of freedom - A.02.

60

TABLE IX

HESULTS OF ANALYSIS OF VARIANCE OF THYROID SECRETION RATE
AMONG GENETICALLY DIFFERENT GROUPS OF MICE
Sources of
Variance

Degree of
Freedom

Sum of
Square s

120

241.81

9

139.85

111

101.97

Total
Genotypes
Error

K - = IT

[ ^ ni

a", =

“

Mean
Squares

F

15-54

16.925

IT ^ 121 ~ 121

.918

“ 11 fr1*9]

= -302

A + P.05
significant differences among different
strains of mice is as follows:
C57BL/6 >
BBFf ^

all other strains hut BBF^

all other strains but C57BL/6 ^ and-f

C57BR/cd^>

C57BR/cd

, A/Jax, BALB/c and CAF^

No difference between A/Jax, BALB/c and CAF^

10

61

SOOOC-

COUNTS

FSR

minute;

6000c‘

xooog

DATS
Fig. 1. 1*088 of the activity of carrier-free I-I31 standard in
counts per minute, drawn on semi-log scale against time
in days(see text).

62

Fraction

of the previous

activity

1.00

^i<r*e

+ i<r£

0.90

0.80

0.70

0.60

*

/
•/

Y* 0.592+ O.I9UX

r xy-0.791
0.50

Standard error »0 099
If Y * 1 .00; X * 2.09 ug.

o.Uo
0:00
Fig. 2* Predicting daily thyroid secretion rate from per cent
of previous count on a group of ordinary mice.

63

1.00

activity

y iw~e.

0.7C

Fraction

of

the

previous

0.80

•X
y * o . 56s + o . i U o X
r^y » 0.90S
Standard error ** 0.069
If Y 3*1.00; X»3.08

0.00

Fig.

0^50---- 1700------ 17^0----- 2705------ 27*55----- TTte
ug. 1-thyroxine/lOO gm. hody weight
'* Predicting daily thyroid secretion rate from per cent of
previous count on a group of ordinary mice.

64
1.00

.90 *

Fraction

of the previous

count

-I's'e.A i<3re
.80

.70

.60

.50 *

T - O . U 5540.l8OX

pxy*0•820
/
/
t
t.
O T ------- ITuO-------- 2700

Standard error«0.091
Ify-SU^i 3L-2.26 ug.

rboJ71

■^TTtT'

ug. 1-thyroxine/100 gm, body weight
Fig.

Predicting daily thyroid secretion rate from per cent of
previous count on a group of ordinary mice.

65

1.00

o.so

previous

count

0.90

of the

, 0.70

Fraction

0.60

T-0.713+0.15SX
0.605
Standard error»0.05^
If Y * 1 .00; X - l .31 ug.

0.50

'O.Uo
T77

“TJT
ug. 1-thyroxine/lOO gm. hody weight

FI g.

^Credicting daily thyroid secretion rate from Der cent
of previous count on a group of ordinary mice.

66

1.00

^ ~ ~i £~t/ jft«-«■

0.80

0.70

Fraction

of the

previous

activity

0.90

0.60
Y - 0.669 + 0 .199X

rjy-0.683
0.50

Standard error * 0.07
If Y * 1 .00; X - 1.26 ug

0.1+0

0T00

0750

0775

Hoo

1.^5

ug. 1-thyroxine/lOO gm. "body weight
Fig.

Predicting daily thyroid secretion rate from per cent of
previous count on a group of ordinary mice.

67

previous

0.70

Fraction

0.80

of the

activity

1.00

o.6o
Y *0.673 +0.150X

-0.892
Standard error * 0.058
If Y * 1 .00; X - 2.18 ug

o.Uo
1.00

0.00

1.50

2.00

ug. 1-thyroxine/100
thyroxine/100 gm. "body weight
n
Fig.

Predicting daily thyroid secretion rate from per cent of
previous count on a group of ordinary mice.

of previous

1 .00'

0.90

Fraction

activity

08

0.80

T - 0 .831+ 0 .096

rxy *0* 785
Standard error « 0.0U7
If T » 1 .00; X » 1.76 ug.

0.70

0.60

0.00

1.00

2.00

ug. 1- thyroxine/100 gra. hody weight
Fig.

#

Predicting daily thyroid secretion rate from per cent
of previous count on a group of ordinary mice.

69

o

o

O O'-'

md

o

•H

>

O M
4, h -

T CVj

®

©
Is
P
u
V
O
4dJ
©
X6I
f* u
u
© ©
p,
*
h

CVi LTN

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o
LT\

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o

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o

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p

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4-»
g
d

o

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d

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w
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©
h
O
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tfl
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XI
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crt

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M
d
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o
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'g
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d
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I
s
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60

JL%\a\%ot3 snoxAsad jo nofijo»ati

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70

00

Fraction

of previous

activity

-i

^

0.90

0.80

0.70A/jax

S

Y*0.7U0+0.12Ux
rxy * 0.817

0.6c-

Standard error -0.05s
If Y » 1 .00; X - 2.09 ug.

0. 5d
0.00
o.oo

0.50

1.00

I.50
1.50

2.00

2.50
50

ug. 1
I-thyroxine/100
-thyroxine/lOO gas. hody
'body weight
Fig.

^

Predicting daily thyroid secretion rate from per cent
of previous count on strain A/jax

3 .00

71

Fraction

of previous

activity

1.00

I*

0.90

0.80

0.70
A/jax
Y* 0.739 +O.IU7X
rxy * 0 .8^5
Standard error * 0 .0^9
If Y * 1 .00; X - 1.77 ug.

0.60

0.50

ot&j

07^0

nrfc

17^0------------------

3700

ug. 1-thyroxine/100 gm. "body weight
Fig.

Predicting daily thyroid secretion rate from oar cent of
previous count on strain A/jax

raction

of previous

activity

1.00

-

0.9 o

0.80

.

0.70

_

V

*
CAFi
Y

0.60

-

<f

O.76I O.O93X
0.515

Standard error 0.060
If Y 1 .00; X 2.56 M g .
0.50
0.00

O.5O

1.00

1.50

2.00

0.50

3.00

ug. l-thyroxine/lOO gra. body weight
Fig.

Predicting daily thyroid secretion rate from per cent of
previous count on strain CAF,

?3

1.00

Fraction

of previous

activity

>
•/

0.80

0.70 CAF1 $
Y ■ O.73? + 0 .160X

0.60 -

rxy*°-732
Standard error**n.oUg
If Y * 1 .00; X « 1.67 ug.

0.50

■"0:5b

h d t S----

ug. l-thyroxine/100 gm. body weight
Fig. ^ 3# Predicting daily thyroid secretion rate from per cent of
previous count on strain

CAF^,

of previous

O.90

0.80

Fraction

activity

1.00

O.70

BALB/c &
Y « 0 .7?9 + 0.117X
rxy =0.75S
Standard error » 0.095
X - 2.07 ug.

0.60

O.5O

0.00

0.50

1.00

1.50

2.00

2.5O

3.00

ug. 1-thyroxine/100 gm. tody weight
Fig.

Predicting daily thyroid secretion rate from per cent
of previous count on strain BALB/c

/)

Fraction

of previous

activity

1.00

O .90

•/
0.80

O.7O
BALB/c £

V
t

rxy
-93^
T — 0.67O + 0.200X
Standard error & 0.027

*

0,60

x«.i.6s

0.50

ortjo----07^0—
ug.
Fig. * ': ? m

"tt6o---- rr^o

?r^o

5700

l-thyroxine/100 gm. b o d y weight

P r e d i c t i n g d a i l y thyroid secretion rate from oer cent of
o revious count on strain BALB/c

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