PROGESTERONE AND SEXUAL DIFFERENTIATION OF THE BRAIN

这项建议解决了一个对研究 心理健康：母婴互动对心理健康的影响 大脑中性别差异的发展。大脑中的性别差异 结构和功能可能是行为差异的基础 在雄性和雌性之间。胎儿睾丸素指导性行为 大脑的分化和随后的行为。然而，胎儿 也暴露于母体孕激素，这种激素很容易跨越 胎盘，并可能存在于母乳中。孕激素受体 胎儿和新生儿视前内侧核的表达 老鼠在雄性中很高，但在雌性中几乎没有。MPN是一个 大鼠大脑中最具性别二型性的结构和中介 几种不同的性行为。这表明母体 黄体酮可能在性行为中扮演着以前被忽视的角色 中枢神经系统的分化。这项建议的主要目的是 阐明孕酮及其受体在发育中的作用 大脑中的性别差异。I和II将涉及的具体目标 关于个体发育和荷尔蒙的先前未解答的问题 胎儿和新生儿脑内孕激素受体的调节。 具体目标三将确定流通之间的关系 胎儿/新生儿及其母亲体内的黄体酮及其经验性 确定母体循环中的黄体酮是否可以通过 胎盘与胎儿神经元内的核受体结合 大脑。具体目标四将考察在公关方面的性别差异是否在 MPN调节已知存在于其他基因表达的性别差异 类固醇受体。特定目标V将检验以下假设 黄体酮在预防程序性卵巢癌中起着重要作用 神经元死亡，一种对性行为至关重要的细胞/分子机制 MPN的分化。这项研究中提出的实验 应用对心理健康也有临床意义。这个 美国妇女的孩子在怀孕期间接受孕激素治疗 为了防止流产，表现出各种心理 和行为影响。然而，围产期的发育影响 对母体孕激素暴露的研究仍然严重不足。结果 可能会极大地改变我们对性行为的看法 大脑中的差异就形成了。通过这项工作和 母亲在儿童性别分化中的重要作用 大脑和行为可能会被揭示。

This proposal addresses an issue critically important to the study of mental health: the effect of the maternal/fetal interaction on the development of sex differences in the brain. Sex differences in brain structure and function presumably underlie behavioral differences between males and females. Fetal testosterone directs the sexual differentiation of the brain and subsequent behavior. However, fetuses are also exposed to maternal progesterone which readily crosses the placenta and is presumably present in mother's milk. Progestin receptor expression in the medial preoptic nucleus (MPN) of fetal and neonatal rats is high in males but virtually absent in females. The MPN is one of the most sexually dimorphic structures in the rat brain and mediates several sexually differentiated behaviors. This suggests that maternal progesterone may play a previously overlooked role in the sexual differentiation of the CNS. The main objective of this proposal is to elucidate the role of progesterone and its receptor in the development of sex differences in the brain. Specific Aims I and II will address previously unanswered questions regarding the ontogeny and hormonal regulation of the progestin receptor in the fetal and neonatal brain. Specific Aim III will determine the relationship between circulating progesterone in fetuses/neonates and their mothers and will empirically determine whether progesterone in maternal circulation can cross the placenta and bind to nuclear receptors within the neurons of the fetal brain. Specific Aim IV will examine if the sex difference in PR in the MPN regulates sex differences known to exist in the expression of other steroid receptors. Specific Aim V will test the hypothesis that progesterone plays an important role in prevention of programmed neuronal death, a cellular/molecular mechanism critical to the sexual differentiation of the MPN. The experiments proposed in this application have clinical implications for mental health as well. The children of women in the U.S. treated with progestins during pregnancy for the prevention of miscarriage, exhibit a variety of psychological and behavioral effects. Yet, the developmental effects of perinatal exposure to maternal progesterone remains grossly understudied. Results from these studies could dramatically change our thinking about how sex differences in the brain are formed. Through this work an influential role of the mother in the sexual differentiation of the brain and behavior may be revealed.