The long-term goal of the proposed studies in this application is to examine the interactions between testicular hormones and pulsatile gonadotropin secretion in an effort to better understand the mechanisms of human male fertility and infertility. The investigators plan to examine pulsatile luteinizing hormone and glycoprotein alpha-subunit secretion in normal men, orchidectomized men, men with testicular failure, and men with idiopathic infertility using intensive blood sampling protocols to understand further the physiology of GnRH secretion. Studies are proposed to determine how pulsatile gonadotropin secretion effects the testis by repetitive sampling of spermatic vein blood for the measurement of testosterone and its precursor steroids in men with varicocele-associated infertility. Their study plan also includes use of dispersed rat pituitary cells stimulated with pulses of GnRH as a model which simulates the normal function of the hypothalamic-pituitary unit to explore questions relevant to human pathophysiology which cannot directly be studied in man. These studies may clarify how testis hormones influence directly the release of gonadotropins by pituitary cells independent of their actions on GnRH. Specifically, they intend to study the feedback actions of androgens and inhibin on FSH, LH and alpha-subunit release by pituitary cells from normal and castrated male rats. Inhibin will be obtained from primate Sertoli cell culture medium. Because human male infertility is a common disorder with no uniformly effective treatment, these studies may provide important information to clinicians and investigators in the fields of physiology, endocrinology, biochemistry, urology and gynecology.
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