Sex Steroids Program Gender Identity

性类固醇计划性别认同

• 批准号: 6867615
• 负责人: THERESA M LEE
• 金额: $ 8.52万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6867615
• 关键词: amygdala; animal developmental psychology; behavior test; behavioral /social science research tag; biological polymorphism; data collection methodology /evaluation; embryo /fetus; female; gender difference; hormone regulation /control mechanism; hypothalamus; immunocytochemistry; mature animal; neuroendocrine system; preoptic areas; radioimmunoassay; receptor expression; sex behavior; sex differentiation; sheep; social behavior; steroid hormone receptor; testosterone; urinalysis; virilism

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.

让女性胎儿接触过量的睾酮（Pren-T）会导致外生殖器男性化，并永久改变中枢神经系统（CNS）对生殖神经内分泌轴和典型性别行为的控制。生殖器男性化的程度并不是睾酮在产前编程的良好指标。识别发育过程中未来性别行为的非生殖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。羊是 这是研究这些关系的绝佳模型，因为实现不同程度的男性化所需的 Pren-T 剂量已经确定，并且青春期前的时间足够长，可以准确评估行为发育，而生殖成熟则在 6-7 个月内发生。由于某些行为的分化在青春期之前就很明显，因此我们建议确定哪些早期行为可以准确预测成年性别行为。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 的时间安排独立于男性化的多种中枢神经系统功能 生殖器，因此男性化的程度不能准确预测行为。此外，一些青少年行为比其他行为更能预测成人的社会性行为。参与社会性行为的关键大脑区域的组织和功能也将由 Pren-T 进行编程。具体目标： 1) 检验 T 的雄激素和雌激素影响会导致青少年性别分化行为，从而预测成年性别二态性行为和神经内分泌功能的假设。 2) 检验以下假设：产后接触雌激素会进一步使接触 Pren-T 的女性行为男性化。 3) 检验 Pren-T 暴露改变杏仁核功能神经解剖学的假设， 视前区和其他两性下丘脑核团。