Exposing female fetuses to excessive testosterone (Pren-T) causes virilization of the external genitalia and permanent alterations in the central nervous system (CNS) control of the reproductive neuroendocrine axis and sex-typical behaviors. The extent of genital virilization is not a good indicator of the prenatal programming by testosterone. Identification of non-genital indicators of future gendered behavior during development would assist pediatricians in developing better treatment protocols for children with ambiguous genitalia. The sheep is an excellent model in which to study these relationships because required doses of Pren-T for achieving varying amounts of masculinization have been determined, and the pre-pubertal period is sufficiently long that behavioral development can be accurately assessed, yet reproductive maturity occurs within 6-7 months. Because differentiation of some behaviors is evident prior to puberty, we propose to determine which early behaviors accurately predict adult gendered behavior. We expect the behavioral differentiation caused by Pren-T to alter steroid hormone receptors, cytoarchitecture and functional responses in key areas of the CNS. Hypothesis: The timing of Pre-T programs a variety of CNS functions independently of virilization of the genitalia, such that the extent ofvirilization does not accurately predict behavior. In addition, some juvenile behaviors will better predict adult social-sexual behaviors than others. The organization and function of key brain areas involved in social-sexual behaviors will also be programmed by Pren-T.
Specific Aims : 1) Test the hypothesis that androgenic and estrogenic affects of T cause juvenile sex-differentiated behaviours that predict adult sexually-dimorphic behaviors and neuroendocrine function. 2) Test the hypothesis that postnatal exposure to estrogen further masculinizes the behavior of females exposed to Pren-T. 3) Test the hypothesis that Pren-T exposure alters the functional neuroanatomy of the amygdala, preoptic area and other sexually-dimorphic hypothalamic nuclei.
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