Sex Steroids Program Gender Identity

使女性胎儿暴露于过量的睾酮(Pren-T)会导致外生殖器男性化，并导致中枢神经系统(CNS)、生殖神经内分泌轴的控制和性典型行为的永久性改变。生殖器男性化的程度不是睾丸激素产前计划的一个很好的指标。确定发育过程中未来性别行为的非生殖器指标将有助于儿科医生为生殖器不明确的儿童制定更好的治疗方案。绵羊是 这是一个研究这些关系的极好的模型，因为已经确定了实现不同数量的男性化所需的Pren-T剂量，并且青春期前的时间足够长，可以准确地评估行为发育，但生殖成熟发生在6-7个月内。由于某些行为在青春期之前就有明显的区别，我们建议确定哪些早期行为可以准确地预测成人的性行为。我们预计Pren-T引起的行为分化会改变中枢神经系统关键区域的类固醇激素受体、细胞结构和功能反应。假设：Pre-T程序的时序与中枢神经系统的各种功能无关 生殖器，所以男性化的程度不能准确地预测行为。此外，一些青少年行为会比其他行为更好地预测成年人的社会性行为。参与社会性行为的关键脑区的组织和功能也将由Pren-T编程。具体目标：1)检验T的雄激素和雌激素效应导致青少年性分化行为的假说，从而预测成人性二态行为和神经内分泌功能。2)检验这样一种假设，即出生后接触雌激素会进一步使接触Pren-T的女性的行为男性化。3)测试Pren-T暴露改变杏仁核功能神经解剖学的假设， 视前区和其他性二型下丘脑核团。

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.