The following dissertation examines the ventromedial nucleus of the hypothalamus (VMH), a brain region that is sexually dimorphic in rodents. The experiments in this dissertation were centered around the question of whether the VMH is sexually dimorphic in mice, and also explored the questions of what the role of circulating testosterone (T) and the androgen receptor (AR) are in this sex difference. The following chapters examine the role of circulating T and the AR in regulating the regional... Show moreThe following dissertation examines the ventromedial nucleus of the hypothalamus (VMH), a brain region that is sexually dimorphic in rodents. The experiments in this dissertation were centered around the question of whether the VMH is sexually dimorphic in mice, and also explored the questions of what the role of circulating testosterone (T) and the androgen receptor (AR) are in this sex difference. The following chapters examine the role of circulating T and the AR in regulating the regional volume, neuron number, neuronal soma size, astrocyte number, and astrocyte complexity in the mouse VMH. The first experiment examines the question of whether sex differences exist in the mouse VMH by looking at unaltered adult male and female mice. The results showed that the VMH is larger in males than females, and that the difference is accounted for by differences in the VL and DM subregions. This experiment also examined sex differences in astrocyte number and complexity in the VMH. The results showed that males have more astrocytes than females in the VMH, and have more complex astrocytes in the VL subregion. Next, we ask if there is a role of circulating T or a functional AR in the VMH sex difference; the next study examines the role of circulating adult T and AR in VMH structure in males, females, and males without a functional AR (iTfm animals). The results showed that VMH volume, specifically of the dorsomedial (DM) and ventrolateral (VL) subregions, was greater in animals with circulating adult T regardless of genotype, including iTfm males, suggesting that T is acting through an AR-independent mechanism. Additionally, neuron number was greater in males and iTfm males as compared to females, suggesting that the sex difference in neuron number is independent of adult circulating T and AR. T treatment did lead to increased neuronal soma size in the VMH, and this response may be dependent on AR, as VMH somata were not significantly different between iTfms with or without adult T treatment. The last experiment examines the question of whether there is a role of AR or circulating T in the astrocyte sex difference using males, females, and iTfm males with and without T treatment to look at astrocyte number and complexity in the VMH. The results show that males and iTfms did not significantly differ in the number of VMH astrocytes, and both had more astrocytes than females. In the VL subregion of the VMH, adult T treatment resulted in more complex astrocytes regardless of genotype or AR status, while no differences were seen in the DM subregion. Together, these experiments show that the VMH is sexually differentiated in mice, with most of the differences being observed in the VL and DM subregions. Additionally, many of these sex differences are due to circulating T acting through an AR-independent mechanism. Show less
