STEROID HORMONES AND FETAL DEVELOPMENT

此应用程序的目的是生成新信息 关于雄激素在细胞水平上的组织作用 两种长孕哺乳动物的大脑，即豚鼠和 恒河猴。 在初步数据的基础上，提出了实验方案。 仔细绘制胞浆雄激素个体发育的变化 这些物种大脑皮层和下丘脑的受体(ARC) 胎儿发育的关键时期，并将这些变化与 雄激素对性反应和性交能力的影响 雄性以循环的方式释放促性腺激素。尝试将 对量化技术进行系统评价 核雄激素受体(ARN)，因为它们不能在 通过常规方法获取胎儿组织。组织的作用 对ARN破坏的蛋白酶也将进行尽可能多的研究 在核基质中的局部化。这项研究建议在 大脑芳构化在性别分化中的作用 将通过使用芳香酶抑制剂来确定 怀孕了。此外，还获得了分子探针，以 恒河猴芳香化酶P-450基因的个体发育研究 胎儿。同样，外源性睾丸素对 使控制促性腺激素释放的周期中心雄激素 在胎豚鼠身上会进行评估。这些研究将 提供有关调节荷尔蒙的细胞事件的新信息 控制大脑发育。

The purpose of this application is to generate new information about the organizing actions of androgen at the cellular level on the brain of two long gestation mammals, the guinea pig and the rhesus monkey. Based on preliminary data, experiments are proposed which will carefully plot changes in the ontogeny of cytosolic androgen receptors (ARc) in the cortex and hypothalamus of these species at critical times in fetal development and relate these changes to the effects of androgen on sexual responsiveness and the capacity of males to release gonadotropins in a cyclic manner. Attempts will be made to systematically evaluate the technique for quantifying nuclear androgen receptors (ARn) since they can not be measured in fetal tissues by conventional means. The actions of tissue proteases on ARn destruction will be studied as well as possible localization within the nuclear matrix. Studies are proposed in which the role of brain aromatization in sexual differentiation will be ascertained by the use of aromatase inhibitors during pregnancy. In addition molecular probes have been obtained to study the ontogeny of mRNA for aromatase P-450 in the rhesus monkey fetus. Likewise, the capacity of exogenous testosterone to androgenize the cyclic centers that control gonadotropin release in the fetal guinea pig will be evaluated. These studies will provide new information on cellular events that mediate hormonal control of brain development.