MALE PSEUDOHERMAPHRODITISM--THE BIOLOGY OF ANDROGENS

男性假两性畸形——雄激素的生物学

• 批准号: 3311085
• 负责人: JULIANNE L IMPERATO-MCGINLEY
• 金额: $ 23.98万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-06-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3311085
• 关键词: Caribbean islands; androstenedione; behavioral genetics; chromatography; developmental genetics; dihydrotestosterone; follicle stimulating hormone; genetic counseling; hormone regulation /control mechanism; human puberty; luteinizing hormone; male; progesterone; pseudohermaphroditism; psychobiology; psychosexual development; regulatory gene; sex differentiation; steroid hormone metabolism; testosterone; tissue /cell culture

Male pseudohermaphrodites, particularly subjects with 5 alpha- reductase deficiency and androgen insensitivity are unique experiments of nature to elucidate the differential effects of testosterone (T) and dihydrotestosterone (DHT) in male sexual differentiation and development as well as other androgen mediated physiologic parameters. The proposed studies of these subjects include; evaluation of the differential effect of T and DHT in the negative feedback control of LH secretion through studies of the pulsatile gonadotrophin secretory profile; definition of the roles of T and DHT in the formation of male gender identity, elucidation of the roles of T and DHT (prenatally and postnatally) on observed sex differences in cognition and lateralization; and definition of the role of DHT on sexual potency in the male. Further animal studies with potent competitive azasteroid inhibitors of the enzyme 5 alpha-reductase to decrease DHT production are planned to further delineate the differential effects of the biologic roles of testosterone and dihydrotestosterone in male sexual differentiation and development. Comparison studies will be carried out with the antiandrogen, flutamide, which blocks the action of both T and DHT. The current proposal includes further studies to define the roles of T and DHT in differentiation of the prostate; the cyclical release of gonadotrophins, spermatogenesis, testicular descent; and sexual behavior of the rat. Studies also include evaluation of the effect of 5 alpha-reductase deficiency on sexual differentiation in the rabbit with particular attention toward defining the role of T and DHT in differentiation of the Wolffian ducts and prostatic differentiation.

男性假两性人，特别是具有 5 α- 的受试者 还原酶缺乏和雄激素不敏感是独一无二的 自然实验来阐明不同的影响 睾酮（T）和二氢睾酮（DHT）对男性性功能的影响 分化和发育以及其他雄激素介导的 生理参数。 这些科目的拟议研究 包括; T 和 DHT 的差异效应评估 通过研究 LH 分泌的负反馈控制 脉动促性腺激素分泌曲线；角色的定义 T和DHT在男性性别认同形成中的作用，阐明 T 和 DHT（产前和产后）对观察到的作用的研究 认知和偏侧化方面的性别差异；和定义 DHT 对男性性能力的作用。 强效竞争性氮杂类固醇的进一步动物研究 5α-还原酶抑制剂可减少 DHT 计划生产以进一步划定差异 睾酮的生物学作用的影响 二氢睾酮在男性性别分化和发育中的作用。 将与抗雄激素药物进行比较研究， 氟他胺可阻断 T 和 DHT 的作用。 目前的 提案包括进一步研究以确定 T 和 DHT 的作用 前列腺的分化；的周期性释放 促性腺激素，精子发生，睾丸下降;和性的 老鼠的行为。 研究还包括效果评估 5α-还原酶缺乏对性别分化的影响 兔子特别注意定义 T 和 DHT 在沃尔夫管和前列腺分化中的作用 差异化。