Hyperandrogenemia, Diet and Female Reproductive Health

描述(由申请者提供)：俄勒冈健康与科学大学(OHSU)的俄勒冈国家灵长类研究中心(ONPRC)提议成立一个专门的生殖和不孕研究合作中心(U54)，以解决高雄激素血症和肥胖对女性生殖健康的影响。一项跨学科的翻译计划旨在区分过量雄激素暴露和典型西式饮食(WSD，高脂肪和果糖含量)导致的代谢变化对以下方面的影响：(1)下丘脑-垂体-卵巢-生殖道轴，以及脂肪组织；(2)对生育的影响；(3)治疗效果是否可逆。三个研究项目使用非人类灵长类动物模型，一个项目专注于患有多囊卵巢综合征(PCOS)的瘦弱女性的特定人群。项目一，“代谢和神经内分泌对高雄激素血症和饮食的反应”，由J.卡梅伦指导，由匹兹堡大学和ONPRC的K.Grove组成的财团共同完成。项目II，《卵巢和子宫结构-功能：雄激素和饮食的影响》，是R.Stouffer和 O.斯莱登，ONPRC。项目III，“雄激素和饮食对脂肪功能的影响”，涉及C.Roberts和ONPRC的同事。项目四，“雄激素过量作为多囊卵巢综合征女性脂肪生成功能障碍的机制”，与加州大学洛杉矶分校的临床专家(D.Dumesic，G.Chazenbalk)组成了一个联盟。L-11项目将由一个非人类灵长类核心(O·斯莱登，主管)支持，作为一个封闭的资源运行。该中心将维持四组年轻雌性恒河猴的治疗(对照组、睾丸素或T处理、WSD处理和T+WSD)四年，最终在生育试验中达到顶峰。在公元05年，我们会研究水务署和水务署行动的可逆性。此外，行政核心(R.Stouffer，P.I.)和外联核心(D.Gordon和M.Zelinski)将促进SCCPIR中心内部和之间的互动，并提高公众对生殖健康研究的认识和了解。重要的是，与多囊卵巢综合征等生育障碍的病因和治疗有关的雄激素和饮食相关因素单独或联合作用的新信息将会增加。

DESCRIPTION (provided by applicant): The Oregon National Primate Research Center (ONPRC) at the Oregon Health & Science University (OHSU) proposes a Specialized Cooperative Center in Reproduction and Infertility Research (U54) that addresses the effects of hyperandrogenemia and obesity on female reproductive health. An interdisciplinary, translational program is designed to discern between the effects of excess androgen exposure and metabolic changes due to a typical Western-style diet (WSD, high fat and fructose content) on: (1) the hypothalamus-pituitary-ovary-reproductive tract axis, as well as adipose tissue; (2) the impact on fertility; and (3) if the treatment effects are reversible. Three research projects ue the nonhuman primate model, and one project focuses on the specific population of lean women with polycystic ovarian syndrome (PCOS). Project I, "Metabolic and Neuroendocrine Responses to Hyperandrogenemia and Diet", is directed by J. Cameron, via a consortium with the University of Pittsburgh and K. Grove at ONPRC. Project II, "Ovarian and Uterine Structure-Function: Influence of Androgen and Diet", is a collaboration between R. Stouffer and O. Slayden, ONPRC. Project III, "Effects of Androgen and Diet on Adipose Function," involves C. Roberts and colleagues at ONPRC. Project IV, "Androgen Excess as a Mechanism for Adipogenic Dysfunction in PCOS Women," incorporates a consortium with clinical experts (D. Dumesic, G. Chazenbalk) at the University of California, Los Angeles. Projects l-lll will be supported by a nonhuman primate (NHP) Core (O. Slayden, Supervisor) operating as a closed resource. This Core will maintain four treatment groups of young, female rhesus monkeys (controls, testosterone or T-treated, WSD-treated, and T + WSD) for four years, culminating in a fertility trial. In Year 05, reversibility of T and WSD actions will be examined. In addition, the Administrative Core (R. Stouffer, P.I.), and Outreach Core (D. Gordon and M. Zelinski) will promote interactions within and among SCCPIR Centers and increase public awareness and understanding of reproductive health research. Important, new information will accrue on the actions of androgen and diet-related factors, individually and in combination, relevant to the etiology and treatment of fertility disorders, such as PCOS.