BRAIN AROMATASE ACTIVITY AND REPRODUCTIVE FUNCTION

此应用程序的目的是生成有关 脑芳香化酶活性（AA）的定位及其控制 非人类灵长类动物和实验室啮齿类动物中的雄激素。 在上一个赠款期间，我们描述了AA的分布， 猴和大鼠大脑，并提供了雄激素依赖性和 独立的控制机制。 我们证明了AA和AR是 不均匀地分布在大脑的离散区域， 它们共定位在相同的区域，从而提供了细胞成分， 雄激素才能发挥作用 大脑中的芳香酶活性 去势后下降， 雄激素治疗 在此更新应用程序中，我们希望延长 这项工作在第一个资助期就开始了， 细胞事件的基础上的生物功能的AA在 哺乳动物的大脑 我们假设，对反馈动作的不应性状态 T对促性腺激素分泌的影响，我们在恒河猴中观察到， 由于雌激素缺乏而发生阉割。 我们的实验将 解决了原位雌激素产生的生理作用 非人灵长类和啮齿类动物以及啮齿类动物促性腺激素控制 性行为 使用芳香酶P-450和AR的分子探针， 我们希望利用分子生物学的工具 探讨雄性大鼠肾上腺皮质激素受体mRNA和AR的分布和调控 和恒河猴。 我们希望通过这种方式阐明一些步骤 这构成了雄激素与其受体结合之间的“灰色地带”， 以及AA的诱导。 最后，我们怀疑，一系列复杂的相互作用存在于 雌激素在神经系统内的原位产生， AR的合成和激活以及雄激素的诱导作用 在AA。 拟议的实验解决了其中一些问题。

The purpose of this application is to generate new information about the localization of brain aromatase activity (AA) and its control by androgen in nonhuman primates and laboratory rodents. In the previous grant period we described the distribution of AA in monkey and rat brains and provided evidence for androgen dependent and independent control mechanisms. We demonstrated that AA and AR are heterogeneously distributed in discrete regions of the brain and that they colocalize in the same areas, thus providing a cellular component for androgens to exert their effects. Aromatase activity in the brain decreased after castration and was restored to normal levels following androgen treatment. In this renewal application we hope to extend the work begun in the first grant period to include experiments that probe the cellular events that underlie the biological function of AA in the mammalian brain. We hypothesize that the state of refractoriness to the feedback action of T on gonadotropin secretion that we observed in rhesus monkeys after castration occurs because of estrogen deficiency. Our experiments will address the physiological role of in situ estrogen production in gonadotropin control in nonhuman primates and rodents and in rodent sexual behavior. Using molecular probes for aromatase P-450 and AR that are now available to use we hope to use the tools of molecular biology to investigate the distribution and control of mRNA and AR in male rats and rhesus monkeys. In this way we hope to elucidate some of the steps that constitute the "gray area" between androgen binding to its receptor and the induction of AA. Finally, we suspect that a complex series of interactions exists between the in situ production of estrogen within the nervous system, the synthesis and activation of the AR and the inductive effects of androgen on AA. the proposed experiment address some of these issues.