STEROID HORMONES AND FETAL DEVELOPMENT

在前几年，我们调查了类固醇激素环境 非人灵长类动物的胎儿发育。随后，我们提供了证据，证明 胎儿性腺和垂体之间的长环负反馈 腺体是在胎儿时期建立的，双氢睾酮(DHT)可以 成为反馈环路的一部分。在这项拨款申请中，我们建议 通过集中精力研究神经对雄激素的处理来继续这项工作 组织，被认为是雄激素在性别分化中的作用部位。二 将对加工的各个方面进行研究。首先，我们将调查 5Alpha-R还原酶(5Alpha-R)活性在整个生育期的分布 中枢神经系统(CNS)和比较男性这种活动的特点 和雌性。一旦知道了这一活动的轨迹，我们将研究它的 个体发育和控制，并将试图“精确定位”5Alpha-R在 特定的大脑核团。将对胎儿恒河猴进行比较 猕猴和豚鼠，另一种长期妊娠的哺乳动物，对它们的相似 目前还没有数据。 这项工作的第二个主要推动力将是建立 在胚胎猴子和胚胎豚鼠中都含有雄激素受体。 先前对大鼠的观察表明，脑雄激素的测量 受体为性交“关键期”的开始提供了标志物 差异化。我们计划研究大脑雄激素受体的个体发育 在胚胎猴子和豚鼠身上，意在获得新的 关于雄激素依赖发育期开始的信息。 完成的实验将提供重要的新信息 神经组织在雄激素处理时的细胞事件 性别分化。

In previous years, we investigated the steroid hormone milieu in which nonhuman primate fetuses develop. Subsequently, we provided evidence that long-loop negative feedback between the fetal gonads and the pituitary gland is established in fetal life and that dihydrotestosterone (DHT) can be a component of the feedback loop. In this grant application, we propose to continue this work by concentrating on androgen processing by neural tissue, a presumed site of androgen action in sexual differentiation. Two facets of the processing will be studied. First, we will investigate the distribution of 5Alpha-R reductase (5Alpha-R) activity throughout the central nervous system (CNS) and compare features of this activity in males and females. Once the loci for this activity is known, we will study its ontogeny and control, and will attempt to "pinpoint" 5Alpha-R activity in particular brain nuclei. Comparisons will be made between fetal rhesus macaques and guinea pigs, another long-gestation mammal, for which similar data are not yet availabe. The second major thrust of this work will be to establish the loci that contain androgen receptors in both fetal monkeys and fetal guinea pigs. Previous observations in rats suggest that measurements of brain androgen receptors provide markers for the onset of the "critical period" for sexual differentiation. We plan to study the ontogeny of brain androgen receptors in fetal monkeys and guinea pigs with the intention of obtaining new information about the onset of androgen-dependent developmental periods. The completed experiments will provide important new information about cellular events for androgen processing by neural tissue at the time of sexual differentiation.