The general objective of this work is to define carefully the endocrine milieu that is reo/Liired 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 answer 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? Does FSH play a role in stimulating steroidogenesis in man? 2. What are the physiological roles of luteinizing hormone (LH) in men? Is LH required to maintain human spermatogenesis? Is the pulsatile nature of LH secretion a physiologically important aspect of the pituitary's stimulatory effect on testicular steroid secretion? 3. Is the conversion of testosterone (T) to dihydrotestosterone (DHT) i.e. 5a 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 does 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 5a 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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