The Role of Progesterone Receptor in Neural Development

类固醇激素在神经发育的基本过程中发挥着巨大的作用，特别是在大脑功能和行为的性别差异的发展中。啮齿类动物模型表明，在神经发育的关键时期，男性大脑的某些区域可能对孕激素更敏感（即孕激素受体（PR）的表达水平更高），这表明孕激素和PR可能在男女大脑和行为的差异发育中起重要作用。利用传统大鼠模型和缺乏功能性PR表达的转基因小鼠，本研究验证了围产期PR的性别差异是大脑性别分化所必需的假设，特别是介导成年期性别分化的生殖和攻击行为的内侧视前核（MPN）。目的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的性别分化过程的理解，以及成年期男性和女性典型行为表型的发育机制。这个研究项目将很好地将研究和教育结合起来，让高度多样化的学生群体参与这些研究的各个方面。此外，交互式网络资源的开发将得到开发，其中将汇编和组织有关核激素受体在发育组织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共享信息并建立否则不可能的合作。

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.