BRAIN AROMATASE ACTIVITY AND REPRODUCTIVE FUNCTION

在这项提案中，我们计划研究控制 中枢神经系统（CNS）中的芳构化。 初步数据 表明啮齿类动物脑芳香化是由睾酮控制的。 现在，我们将定位这种活动的特定区域和核的 CNS，研究激素作用的特异性及其诱导阈值 类固醇激素的作用 芳香化酶活性（AA）的进一步分析将在下文中描述。 在拟议的研究中获得，这些研究将调查 雄激素受体，用于雄激素对脑AA的诱导作用。 我们 假设AA在CNS的不同部位受到不同的控制 并且不同种类的酶复合物是区域性分布的 在大脑中。 实验提出，将调查这些 可能性 首先在啮齿动物身上进行的一些研究将扩大到 包括非人类灵长类动物（Macaca mulatta）。 在灵长类动物研究中， 定位中枢神经系统内的芳香化酶，并确定去势的影响 和雄激素替代对其活性的影响。 我们想知道AA和 通过RIA定量的GnRH位于相同的脑区域内。 我们 已经开发出一种新的抗GnRH的抗血清，似乎有希望为这些 问题研究 一项发育研究提出，胎盘芳香化酶 将被溶解并通过柱色谱法纯化。 抗体将 目的是在某些情况下进行免疫细胞化学， 未来的日期 在啮齿类动物中产生的数据将是重要的 对内分泌方面现有文献（数量很少）的补充 控制大脑芳香化的因素。 灵长类动物的研究 重要的是因为：a）它们代表了第一次真实的尝试来识别 控制机制的芳香化酶和它们的区域内的分布 非人类灵长类动物的大脑

In this proposal we plan to study endocrine factors that control aromatization in the central nervous system (CNS). Preliminary data suggest that brain aromatization in rodents is controlled by testosterone. Now we will localize this activity to specific regions and nuclei of the CNS, study specificity of hormone action and thresholds for its induction by steroid hormones. Further analysis of aromatase activity (AA) will be obtained in proposed studies that will investigate the necessity of androgen receptors, for the inductive action of androgen on brain AA. We postulate that AA is controlled differently in different parts of the CNS and that different species of the enzyme complex are distributed regionally within the brain. Experiments are proposed that will investigate these possibilities. Some studies performed first on rodents will be expanded to include nonhuman primates (Macaca mulatta). In the primate studies we will localize aromatase within the CNS and determine the effects of castration and androgen replacement on its activity. We wish to know whether AA and GnRH quantified by RIA are localized within the same brain regions. We have developed a new antisera to GnRH that appears promising for these studies. A developmental study is proposed in which placental aromatase will be solubilized and purified by column chromatography. Antibodies will be produced with the intent of performing immunocytochemistry at some future date. The data that will be generated in rodents will be important additions to the existing literature (which is quite small) on endocrine factors that control aromatization in the brain. The primate studies are important because: a) They represent the first real attempt to identify control mechanisms for aromatase and their regional distribution within the brain of non-human primates.