Understanding how sex differences arise at the neuroanatomical level may help us develop new treatments for conditions like depression and anxiety that are strongly gender-biased. The current proposal is aimed at determining the role of the androgen receptor (AR) in regulating the morphology of two sexually dimorphic brain areas, the posterodorsal medial amygdala (MePD) and the posteromedial bed nucleus of the stria terminalis (BNSTpm), during puberty and adulthood. For several decades, it has been thought that masculine brain development in mammals is regulated by the action of estrogen (E) derived from the aromatization of testosterone (T), and that sexual differentiation of the brain occurs only around the time of birth and is permanent. Recent studies, however, contradict both of these paradigms. The MePD and BNSTpm, which are larger in males than females, and are important in mating and emotional behavior, retain a high degree of plasticity in adulthood. Specifically, MePD volume is feminized by castration in adult males, while the BNSTpm volume is reduced by roughly 28%. This decrease in volume can be rescued by treating male castrates with E. However, male rats with the testicular feminization mutation (Tfm) that lack a functional AR have MePD and BNSTpm volumes that are intermediate between wild-type males and wild- type females, suggesting that AR is also important. Interestingly, while sexual dimorphisms in volume and somal area remain plastic in adulthood in the MePD, neuron number does not, suggesting that this parameter is permanently organized during development. I propose a set of experiments aimed at 1) determining whether demasculinization of the BNSTpm in Tfm males rats results from a decrease in neuronal number 2) determining whether the sexual dimorphism in neuron number in these regions occurs during puberty 3) determining the cellular mechanisms responsible for this sexual dimorphism in neuron number.
