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)的芳构化。初步数据 表明啮齿动物大脑的芳香化是由睾酮控制的。 现在我们将这一活动定位到特定的区域和核 中枢神经系统，研究激素作用的特异性及其诱导阈值 由类固醇激素引起的。芳香酶活性(AA)的进一步分析将 在拟议的研究中获得，该研究将调查 雄激素受体，用于雄激素对脑AA的诱导作用。我们 假设AA在中枢神经系统的不同部分受到不同的控制 不同种类的酶复合体在区域上分布 在大脑里。有人提议进行实验，以研究这些 可能性。一些首先在啮齿动物身上进行的研究将扩大到 包括非人灵长类(猕猴)。在灵长类动物研究中，我们将 确定芳香酶在中枢神经系统内的位置并确定去势的影响 和雄激素替代对其活性的影响。我们想知道机管局和 RIA定量的GnRH定位于相同的脑区。我们 已经开发出一种新的GnRH抗血清，对这些似乎很有希望 学习。提出了一项发育研究，其中胎盘芳香酶 将通过柱层析进行增溶和纯化。抗体会 目的是为了在某些地方进行免疫细胞化学 未来的日期。在啮齿动物身上产生的数据将是重要的 对现有的关于内分泌的文献(相当少)的补充 控制大脑芳构化的因素。灵长类动物的研究是 重要的原因是：a)它们是第一次真正尝试确定 芳香酶的调控机制及其在土壤中的区域分布 非人灵长类动物的大脑。

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.