Clinical and Basic Studies in Polycystic Ovarian Syndrome

描述(由申请人提供)：弗吉尼亚大学拟建的U54中心的主要目标是促进转化性研究，从而将新的基本发现应用于临床。中心主题是“多囊卵巢综合征的临床和基础研究”。这一主题符合合作中心计划的目标，因为目前对无排卵和代谢异常的疾病的治疗方法疗效有限，重要的是，多囊卵巢综合征的基本机制仍不确定。目前关于PCOS病因的假说主要集中在对GnRH分泌和作用的调节，和/或卵巢功能紊乱，其本质上或由于促性腺激素或辅促性腺激素如胰岛素和IGF-1的异常刺激所致。U54中心提出1个临床项目、1个临床试点项目和2个相关基础项目来研究这些地区。项目I解决了正常和肥胖青春期女孩GnRH脉冲发生器调节中的异常(睾酮引起的黄体酮作用抵抗)，并与项目II、GnRH-促性腺激素反应的调节-类固醇-代谢相互作用的基础研究和项目III关于GnRH神经元控制中的类固醇-代谢相互作用的基础研究直接相关。该试点项目是一个临床项目，旨在解决青春期女孩肥胖相关高雄激素血症的决定因素。中心的次级项目得到两个核心的支持，这些核心拟在“开放获取”模式下运作。研究的总体整合将由管理核心执行，具体的实验室服务将通过配基分析和分析核心向U54项目和合格的RSB项目资助的RSB计划相关项目提供，后者已被RSB指定为国家资源。拟建的U54中心将建立在弗吉尼亚大学现有U54中心富有成效的大学氛围基础上，并允许临床和基础调查生殖年中一种常见女性疾病的病因。基础和临床项目的结合将使基本信息能够迅速转化为临床应用，总体目标是提高我们预测青少年疾病的能力，并改进多囊卵巢综合征的治疗方法，从而改善美国约6%-8%的妇女的健康状况。

DESCRIPTION (provided by applicant): The proposed U54 Center at the University of Virginia will have a major goal of promoting translational research leading to application of new basic findings to clinical application. The Center theme is "Clinical and Basic Studies in Polycystic Ovarian Syndrome (PCOS)". This topic is appropriate to the goals of the Cooperative Centers Program, in that present therapeutic approaches to the anovulation and metabolic abnormalities in the disorder are of limited efficacy, and importantly, the basic mechanisms underlying PCOS remain uncertain. Current hypotheses as to of the etiology of PCOS center on regulation of GnRH secretion and action, and/or disordered ovarian function, either primary in nature or consequent to abnormal stimulation by gonadotropins or co-gonadotropins such as insulin and IGF-1. The U54 Center proposes 1 clinical project, 1 clinical pilot project, and 2 related basic projects to investigate these areas. Project I addresses abnormalities (testosterone induced resistance to progesterone action) in the regulation of the GnRH pulse generator in normal and obese adolescent girls and is directly related to basic studies in Projects II, modulation of GnRH-Gonadotrope responses - steroid-metabolic interactions, and Project III on steroid-metabolic interactions in the control of GnRH neurons. The pilot project is a clinical project addressing factors determining obesity-associated hyperandrogenemia in peripubertal girls. The Center subprojects are supported by two Cores proposed to operate under an "open access" formula. Overall integration of the research will be performed by the Administration Core, and specific laboratory services will be available to U54 projects and to eligible funded RSB program relevant projects through the Ligand Assay and Analysis Core, the latter having been designated a national resource by the RSB. The proposed U54 Center will build on the productive collegial atmosphere of the existing U54 Center at the University of Virginia and allow clinical and basic investigation of factors in the etiology of a common disorder of women during the reproductive years. The linking of basic and clinical projects will allow rapid transfer of basic information to clinical application, with the overall goal of enhancing our abilities to predict the disorder in adolescents and to enhance therapeutic approaches to PCOS with a resultant improvement in health for some 6-8% of women in the U.S.