HORMONAL CONTROL OF HUMAN TESTICULAR FUNCTION

人类睾丸功能的激素控制

• 批准号: 6655304
• 负责人: WILLIAM J BREMNER
• 金额: $ 15.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6655304
• 关键词: bioassay; biopsy; blood tests; clinical research; dihydrotestosterone; enzyme inhibitors; fertility; follicle stimulating hormone; genetic regulation; gonadotropin releasing factor; gonadotropins; hormone inhibitor; hormone regulation /control mechanism; human middle age (35-64); human subject; luteinizing hormone; male; recombinant proteins; spermatogenesis; spermatogenesis inhibitor; steroid biosynthesis; testis; testosterone; testosterone 5 alpha reductase; young adult human (21-34)

The general objective of this work is to define carefully the endocrine milieu that is required to maintain normal testicular function in men. In particular, we are concerned with the gonadotropin and steroid environment necessary to stimulate human spermatogenesis and steroidogenesis. We will be experimentally manipulating the hormonal environment of the testis in normal men and determining the resultant effects on spermatogenesis and steroid production. More specifically, the objectives of this work are to anser questions in four areas: 1. What are the physiological roles of follicle-stimulating hormone (FSH) in men? Is FSH required to maintain spermatogenesis in man? 2. What are the physiological roles of luteinizing hormone (LH) in men? Is LH required to maintain human pituitary stimulatory effect on testicular steroid secretion? 3. Is the conversion of testosterone (T) to dihydrotestosterone (DHT) i.e. 5alpha reduction, important in the stimulation of human spermatogenesis? What are the concentrations of T and DHT in the human testis in various experimental paradigms, and doses this information advance our understanding of the control of spermatogenesis. 4. Can the new gene array technology be applied successfully to studies of the human testis; if so, will this new technology yield additional insights into the genes controlling human spermatogenesis and steroidogenesis? This work will make use of new compounds, including recombinant human FSH and LH, a gonadotropin releasing hormone (GnRH) antagonist and a 5alpha reductase inhibitor, for exploring the normal physiologic control systems of human testicular function. Our studies are directly relevant to the development of safe, effective, reversible methods of male contraception and to the treatment of men disorders of spermatogenesis.

这项工作的总体目标是仔细定义维持男性正常睾丸功能所需的内分泌环境。我们特别关注刺激人类精子发生和类固醇生成所需的促性腺激素和类固醇环境。我们将通过实验操纵正常男性睾丸的激素环境，并确定其对精子发生和类固醇产生的影响。更具体地说，这项工作的目标是回答四个领域的问题： 1. 卵泡刺激素 (FSH) 对男性的生理作用是什么？ FSH 是维持人类精子发生所必需的吗？ 2. 黄体生成素（LH）对男性有什么生理作用？ LH 是否需要维持人类垂体对睾丸类固醇分泌的刺激作用？ 3. 睾酮 (T) 转化为二氢睾酮 (DHT)，即 5α 减少，对于刺激人类精子发生重要吗？在各种实验范式中，人类睾丸中 T 和 DHT 的浓度是多少，这些信息加深了我们对精子发生控制的理解。 4. 新的基因芯片技术能否成功应用于人体睾丸的研究？如果是这样，这项新技术是否会对控制​​人类精子发生和类固醇生成的基因产生更多的见解？这项工作将利用新化合物，包括重组人 FSH 和 LH、促性腺激素释放激素 (GnRH) 拮抗剂和 5α 还原酶抑制剂，探索人类睾丸功能的正常生理控制系统。我们的研究与安全、有效、可逆的男性避孕方法的开发以及男性精子发生障碍的治疗直接相关。