HORMONAL CONTROL OF HUMAN TESTICULAR FUNCTION

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。特别是，我们关注的是促性腺激素和类固醇环境，这是刺激人类精子发生和类固醇生成所必需的。我们将在实验中操纵正常男性睾丸的激素环境，并确定由此产生的对精子发生和类固醇产生的影响。更具体地说，这项工作的目的是在四个方面回答问题：1.卵泡刺激素(FSH)在男性中的生理作用是什么？促黄体生成素(FSH)是维持人类精子发生所必需的吗？2。黄体生成素在男性中的生理作用是什么？黄体生成素是否需要维持人类脑下垂体对睾丸类固醇分泌的刺激作用？3.睾酮(T)转化为双氢睾酮(DHT)，即5α还原，在刺激人类精子发生中是否重要？在不同的实验范例中，T和DHT在人类睾丸中的浓度是多少，这些信息是否有助于我们理解精子发生的控制。4.新的基因阵列技术能否成功地应用于人类睾丸的研究；如果是的话，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？这项工作将利用新的化合物，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，来探索人类睾丸功能的正常生理控制系统。我们的研究直接关系到安全、有效、可逆的男性避孕方法的发展以及男性精子发生障碍的治疗。

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.