ACTION OF HORMONES ON PROTEIN AND RNA METABOLISM

提供对雄激素正常作用途径的洞察 胚胎和胚胎后的生命，以及通过 雄激素作用受损可能导致疾病，实验将是 针对雄激素作用的三个主要阶段- 雄激素与受体的结合，5α-睾酮还原为 双氢睾酮和雄激素芳构化为雌激素。在……里面 关于雄激素受体，我们将分析其分子缺陷。 选定的具有损害受体功能的突变的患者会发生 改进的功能和遗传技术用于诊断和追踪 雄激素受体突变的遗传，定义了对照 调节雄激素受体基因表达的元件，以及 探讨不同年龄组大鼠雄激素受体水平的调节 雄激素靶组织。提供对以下角色的深入了解 双氢睾酮在雄激素生理学中的形成，我们将进行研究 双氢睾丸酮的形成放大 体内和体外系统中的雄激素信号。定义…的角色 雄激素的雌激素代谢产物在雄激素中的作用，我们分析了 正常卵巢和正常卵巢芳香化酶起始点的性质 腺外雌激素形成的组织(脑)，并研究 组织特异性基因表达调控机制的研究进展 其中芳香酶的控制被取消排列的睾丸细胞系。在……里面 总结，我们将利用生理学、遗传学、内分泌学和 雄激素作用的分子分析技术及其应用 病理生理学。这些研究与人类疾病有直接关系- 对于常见的出生缺陷，如尿道下裂和 男性少见疾病中的性别分化 雄激素抵抗所致的假两性畸形。

To provide insight into the normal pathway of androgen action during embryonic and, postembryonic life and into the mechanism by which impairments of androgen action can result in disease, experiments will be addressed to each of the three principal phases of androgen action - binding of androgen to the receptor, 5alpha-reduction of testosterone to dihydrotestosterone, and aromatization of androgen to estrogen. In regard to the androgen receptor, we will analyze the molecular defects in selected patients with mutations that impair receptor function, develop improved functional and genetic techniques for diagnosing and tracing the Inheritance of mutations of the androgen receptor, define the control elements that regulate expression of the androgen receptor gene, and Investigate the regulation of androgen receptor levels in different androgen target tissues. To provide insight into the role of dihydrotestosterone formation in androgen physiology, we will Investigate the mechanism by which dihydrotestosterone formation amplifies the androgen signal In vivo and in in vitro systems. To define the role of the estrogenic metabolites of androgen in androgen action, we analyze the nature of the start sites for aromatase in normal ovary and a normal tissue in which extraglandular estrogen is formed (brain) and study the mechanism of the control of tissue-specific gene expression in a testicular cell line in which the control of aromatase is derranged. In summary, we will utilize physiological, genetic, endocrinological, and molecular techniques for analysis of androgen action and its pathophysiology. These studies have direct relevance to human disease - both for common birth defects such as hypospadias and for impairment of sexual differentiation in the less common disorders of male pseudohermaphroditism due to androgen resistance.