The identification of anatomical sexual dimorphisms in several forebrain regions of the rat has led to the general view that the sexual differentiation induced by gonadal steroids in these regions may relate to neural mechanisms that underlie sex specific reproductive functions such as copulatory behavior or gonadotropin secretion. An ongoing project involves defining the detailed organization of connections between sexually dimorphic regions of the forebrain known to play a role in modulating reproductive function and our current focus is on the connections of the anteroventral periventricular nucleus (AVPV). The AVPV is located just caudal to the vascular organ of the lamina terminalis and appears to be a nodal point in neural pathways regulating gonadotropin secretion, and provides direct projections to regions that are thought to participate in regulating the release of gonadotropins. By using axonal transport methods combined with immunohistochemistry and confocal microscopy, we determined that the AVPV receives a dramatically sexually dimorphic projection from the principal bed nucleus of the bed nuclei of the stria terminalis which is virtually absent in females. The development of this pathway was studied using axonal labeling methods which showed that this connection is established between postnatal days 9 and 10, but in females does not develop beyond a weak connection. Other projections of the bed nuclei do not display the same degree of dimorphism, suggesting that sex steroid hormones influence the density of connections in a target specific way. Sex steroid hormones also regulate the development of sexually dimorphic populations of neurons in the AVPV. By using mice that have mutations in either the estrogen receptor (ER) or androgen receptor (AR), we have determined that sexual differentian of dopaminergic neurons in the AVPV is dependent on an intact ER, but appears to be independent of the AR. Moreover, we used organotypic explants of the AVPV in vitro to demonstrate that estradiol acts directly on the AVPV. This work has provided a sound framework for similar studies in the rhesus macaque. We are currently using a new explant culture method to study how hormones regulate development of connections and neuronal differentiation in the cerebral cortex perinatal rhesus macaques.
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