STEROID HORMONES AND FETAL DEVELOPMENT

此应用程序的目的是生成新信息 雄激素在细胞水平上的组织作用， 两种妊娠期长的哺乳动物的大脑，豚鼠和 恒河猴 根据初步数据，提出了实验， 仔细绘制胞浆雄激素的个体发育变化 受体（ARc）在这些物种的皮层和下丘脑， 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功能的影响 雄性以循环方式释放促性腺激素。 尝试将 系统地评估量化技术， 核雄激素受体（ARn），因为它们不能在 胎儿组织通过常规方法。 组织的活动 蛋白酶对ARn的破坏将尽可能进行研究 在核基质中的定位。 研究建议， 大脑芳香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 此外，还获得了分子探针， 恒河猴芳香化酶P-450 mRNA的个体发育研究 胎儿 同样，外源性睾酮的能力， 使控制促性腺激素释放的环状中心雄激素化 将对胎豚鼠进行评价。 这些研究将 提供了新的信息，细胞事件，介导激素 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.