DESCRIPTION: (Adapted from applicant's application) The proposed U54 Center at 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 hypothesis as to the etiology of PCOS center around 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 2 clinical and 2 related basic projects to investigate these areas. Project I addressed potential abnormalities in regulation of the GnRH pulse generator and is directly related to Project II, on cellular mechanisms of GnRH frequency regulation of gonadotropin gene expression. Project IV (contract with Virginia Commonwealth University), addresses the clinical effects of reduction of hyperinsulinemia on metabolic profiles and ovulation. Project V is directly related, addressing the mechanism of IGF-1 and LH synergism on ovarian theca cells. The Center subprojects are supported by 4 cores proposed to operated 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 molecular biology, cell science and ligand assay and analysis cores.