BRAIN AROMATASE ACTIVITY AND REPRODUCTIVE FUNCTION

此应用程序的目的是生成有关 脑芳香酶活性(AA)的定位及其调控 非人灵长类动物和实验室啮齿动物中的雄激素。 在之前的授权期中，我们描述了Aa在 猴子和大鼠的大脑，并为雄激素依赖和 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，并且 它们共同位于相同的区域，因此提供了一个蜂窝组件 使雄激素发挥其作用。大脑中的芳香酶活性 去势后下降，之后恢复到正常水平 雄激素治疗。在这次续期申请中，我们希望延长 在第一个授权期内开始的工作，包括探索 构成AA生物功能基础的细胞事件 哺乳动物的大脑。 我们假设反馈作用的不稳定状态 T对恒河猴促性腺激素分泌的影响 去势是由于雌激素缺乏所致。我们的实验将 阐述了原位雌激素产生的生理作用 非人灵长类、啮齿动物和啮齿动物促性腺激素的调控 性行为。使用芳香酶P-450和AR的分子探针 现在可以使用我们希望使用的分子生物学的工具 大鼠肾上腺皮质激素受体和信使核糖核酸的分布及调控 还有恒河猴。我们希望通过这种方式来阐明一些步骤。 构成雄激素与其受体结合的“灰色地带” AA的诱导。 最后，我们怀疑存在一系列复杂的相互作用 神经系统内雌激素的原位产生， 雄激素受体的合成和激活及雄激素的诱导作用 戒酒协会。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.