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. We will be experimentally manipulating the hormonal environment of the testis in normal men and determining the resultant effects on spermatogenesis. More specifically, the objectives of this work are to answer four questions: 1. Can the combination of a gonadotropin-releasing hormone (GnRH) antagonist plus testosterone (T) suppress gonadotropin secretion and thereby spermatogenesis more completely that can T alone? 2. Is the conversion of T to dihydrotestosterone (DHT) i.e. 5alpha reduction, important in the stimulation of human spermatogenesis? 3. Is the conversion of T to estradiol (E2), i.e. aromatization, important in the control of human sperm production? 4. What is the effect of supraphysiologic follicle-stimulating hormone (FSH) stimulation on human testicular function? This work will make use of new compounds, such as a 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 with disorders of spermatogenesis.
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