PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE PRIMATE GONAD

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The mission of the proposed Specialized Cooperative Center in Reproduction at the University of Pittsburgh Medical School is to study, by integrating molecular, cellular and system approaches, the physiological mechanisms that govern gonadal function in primates, and to investigate the pathophysiological bases of specific states of human infertility where parallel and interactive studies of non-human primates are likely to be particularly rewarding. This mission reflects the long- standing forte of this Center to employ non-human primate models to better understand the physiology of reproduction in man. The Center will be comprised of 3 Technical Service Cores (Primate, Assay and Cell Imaging) with an open access format to subserve U54 Projects and additional programs supported by either R01 (7) or R29(1) grants. The U54 Projects focus on the control of gonadal function in primates. Conceptually, they are tightly linked by the theme that FSH plays a fundamental role in the regulation of both ovarian and testicular function, and that the study of the control, and mechanism of action, of this gonadotropin will provide insight into treatment of infertility in men and women. Moreover, it is anticipated that advance sin one project will impact upon the others, and this is exemplified by projects I and II. The first of which will examine the roles of hyperinsulinemia and hyperandrogenemia in producing aberrant patterns of gonadotropin secretion (increased LH:FSH ratios in association with elevated LH pulse frequency) and anovulation in women with polycystic ovarian syndrome. This clinical endeavor is placed in tandem is placed in tandem with a project employing a non-human primate model to examine the action of insulin and androgen on the pituitary/ovarian axis in normal ovulatory monkeys. The remaining U54 projects also employs non-human primate model. It examines the control mechanism whereby sperm production is governed by the FSH-inhibition B feedback loop.