ACTION OF HORMONES ON PROTEIN AND RNA METABOLISM

为了深入了解雄激素作用的正常途径， 胚胎期和胚后期的生活，以及各种方式， 雄激素的作用可能导致疾病状态，各种实验 都计划好了 雄激素受体的抗独特型抗体将是 为了更精确地描述损害的突变， 雄激素受体，以及雄激素调节的各个步骤的研究 将在正常和突变成纤维细胞株中产生作用，包括 二氢睾酮-雄激素转化的研究 受体复合物（DHR-R）的DNA结合状态，DHT-R的相互作用 与核基质以及雄激素作用中的受体后事件。 将研究男性泌尿生殖道的表型分化 其具体目标是确定胆管是否为病毒性胆管炎 直接由于雄激素的作用或间接由于一些 激素对睾丸本身的影响。 的分子生物学 5 α-还原酶缺乏症将通过尝试开发一种 5 α-还原酶的有效抗体，通过研究 5 α-还原酶抑制剂对男性泌尿生殖系统发育的影响 道，并通过研究雄激素如何促进精子发生。 将研究作为内分泌器官的性腺的胚胎分化 在大鼠和负鼠性腺的器官培养制备物中以及在小鼠中 携带一条X染色体或性反转突变。 的 外周组织中芳香化酶反应的遗传控制将是 研究利用鸡的母鸡羽化突变作为模型， 用于研究正常卵巢发育和腺外 雌激素形成 最后，我们将探讨雄激素的作用， 受体后水平，研究甲状腺素和DHT相互作用的性质 在小鼠下颌下腺中，对雄激素作用的独特抗性 在某些野生小鼠品系的肾脏中， 小鼠L细胞中的雄激素依赖基因。

To provide insight into the normal pathway of androgen action during embryonic and postembryonic life and into the various ways that impairment of androgen action can result in disease states, a variety of experiments are planned. Anti-idiotypic antibodies to the androgen receptor will be made for the purpose of characterizing more precisely mutations that impair the androgen receptor, and studies of the individual steps in androgen action will be made in normal and mutant fibroblast strains, including investigation of the transformation of the dihydrotestosterone-androgen receptor complex (DHR-R) to the DNA-binding state, the interaction of DHT-R with the nuclear matrix, and the post receptor events in androgen action. Phenotypic differentiation of the male urogenital tract will be studied with the specific goal of determining whether the wolffian ducts virilize directly as a result of androgen action or indirectly as the result of some effect of the hormone on the testis itself. The molecular biology of 5Alpha-reductase deficiency will be investigated by attempting to develop a potent antibody to the 5Alpha-reductase enzyme, by investigating the effect of 5Alpha-reductase inhibition on the development of the male urogenital tract, and by studying how androgens act to promote spermatogenesis. Embryonic differentiation of the gonads as endocrine organs will be studied in organ culture preparations of rat and opossum gonads and in mice carrying either a single X chromosome or the sex reversal mutation. The genetic control of the aromatase reaction in peripheral tissue will be studied utilizing the henny feathering mutation in chickens as a model system for investigating normal ovarian development and extraglandular estrogen formation. Finally, we will explore androgen action at the post-receptor level, studying the nature of thyroxine and DHT interaction in the mouse submandibular gland, the unique resistance to androgen action in kidneys of certain wild-derived mouse strains, and the regulation of androgen-dependent genes in mouse L cells.