The Role of Progesterone Receptor in Neural Development

类固醇激素对神经发育的基本过程产生了巨大的影响，特别是大脑功能和行为的性别差异。啮齿动物模型表明，在神经发育的关键时期，雄性大脑的某些区域可能比雌性更敏感(即表达更高水平的孕酮受体(PR))，这表明黄体酮和孕酮可能在雄性和雌性大脑和行为的差异发育中发挥重要作用。使用传统的大鼠模型和缺乏功能性PR表达的转基因小鼠，目前的提议检验了这一假说，即围产期PR的性别差异对于大脑的性别分化是必需的，特别是在成年后调节性分化生殖和攻击行为的内侧视前核(MPN)。目的是结合遗传学和药理学方法来检查细胞和行为终点的变化。这些研究的结果将极大地增加我们对神经发育中潜在的性别分化过程的理解，以及成年后男性和女性典型行为表型所涉及的发育机制。这项研究项目将很好地将研究和教育与高度多样化的学生群体相结合，这些学生将参与这些研究的所有方面。此外，还将开发基于网络的互动资源，其中将汇编和组织关于核激素受体在组织发育中的作用的已发表文献，研究各种受体和组织的研究人员可以分享信息，建立否则不太可能的合作。

Steroid hormones exert dramatic effects on fundamental processes of neural development, particularly the development of sex differences in brain function and behavior. Rodent models suggest that regions of the male brain may be more sensitive to progesterone (i.e., express higher levels of progesterone receptor (PR)) during critical periods of neural development compared to females, suggesting that progesterone and PR may play an important role in the differential development of brain and behavior in males and females. Using traditional rat models in tandem with transgenic mice that lack expression of functional PR, the current proposal tests the hypothesis that sex differences in PR during perinatal life are required for the sexual differentiation of the brain, specifically the medial preoptic nucleus (MPN) which mediates sexually differentiated reproductive and aggressive behaviors in adulthood. The Aims combine genetic and pharmacological approaches to examine changes in cellular and behavioral endpoints. Results from these studies will vastly increase our understanding of the processes underlying sexual differentiation of neural development and the developmental mechanisms involved in male- and female-typical behavioral phenotypes in adulthood. This research project will lend itself well to the integration of research and education with a highly diverse student population who will participate in all aspects of these studies. In addition, the development of an interactive web-based resource will be developed, in which published literature on the role of nuclear hormone receptors in developing tissues will be compiled and organized, and investigators studying a variety of receptors and tissues can share information and establish otherwise unlikely collaborations.