Influence of Sex and Estrus Cycle on the Sexual Dimorphisms of the Hypothalamic Ventromedial Nucleus: Stereological Evaluation and Golgi Study

Neurons in the ventromedial nucleus of the hypothalamus (VMN) display structural and biochemical sex differences in response to estrogen. Despite this fact, reports on sex differences in the morphology of the VMN are restricted to its volume and synaptic patterning. The aim of this study was to characterize the neuroanatomical sexual dimorphisms in the VMN and to investigate whether endogenous changes in ovarian steroid secretion influence such dimorphisms. The VMN of adult male rats and intact, aged-matched female rats killed on proestrus and diestrus day 1 was examined by using stereological methods applied to conventionally stained sections and Golgi-impregnated material. The VMN contained 55,000 neurons in rats of both sexes, but its volume was, on average, 1.25 times larger in males than in females. The volume was greater in proestrus than in diestrus rats due to parallel changes in the neuronal somatic size. Unlike the dorsomedial division, neurons in the ventrolateral division had longer dendritic trees in proestrus than in diestrus females and males. The spine density was consistently higher in females than in males in both VMN divisions. In addition, in the ventrolateral part the magnitude of the sex differences varied across the estrus cycle, and reached the greatest value when females were in proestrus. The volume of the neuropil was significantly larger in males than in females, and was not affected by the estrus phase. Our results reveal that the magnitude of the neuroanatomical sex differences in the VMN vary across the estrus cycle due to the trophic influence of estrogen upon its neurons. They also show that the fundamental sex difference in the structure of the VMN is accounted for by the neuropil components.