PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE PRIMATE GONAD

拟建的匹兹堡大学医学院生殖专业合作中心的任务是通过整合分子、细胞和系统方法，研究控制灵长类动物性腺功能的生理机制，并研究人类不育特定状态的病理生理基础，其中平行和相互作用的非人类灵长类动物研究可能特别有益。这项任务反映了该中心长期以来的优势，即采用非人类灵长类动物模型来更好地了解人类生殖的生理学。该中心将由3个技术服务核心（灵长类动物、实验和细胞成像）组成，采用开放获取格式，为U54项目和由R01(7)或R29(1)资助的其他项目提供服务。U54项目主要研究灵长类动物性腺功能的调控。从概念上讲，FSH在调节卵巢和睾丸功能方面起着重要作用，对这种促性腺激素的控制和作用机制的研究将为治疗男性和女性不育症提供见解，这一主题与它们密切相关。此外，预计一个项目的进展将影响到其他项目，项目一和项目二就是例证。第一项研究将检查高胰岛素血症和高雄激素血症在多囊卵巢综合征女性促性腺激素分泌异常模式（LH:FSH比值增加与LH脉冲频率升高相关）和无排卵中的作用。这项临床研究与另一项利用非人类灵长类动物模型研究胰岛素和雄激素对正常排卵期猴子垂体/卵巢轴的作用的项目同时进行。其余的U54项目也采用非人类灵长类动物模型。它检查了精子生产由fsh抑制B反馈回路控制的控制机制。

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.