This career development grant will prepare the candidate to pursue her goal of becoming an independently funded academician devoted to investigating the pathophysiology of Polycystic Ovary Syndrome (PCOS). The poorly understood syndrome of PCOS affects 5-8% of reproductive age women and results in infertility as well as an increased risk of diabetes and heart disease. The long term objective of this proposal is to improve understanding of the pathophysiology of PCOS in order that more effective treatments can be developed. The novel research proposed in this application benefits from mentoring by a strong, multidisciplinary team of senior investigators and uses a new growth hormone antagonist as a physiological probe. The growth hormone antagonist offers the first opportunity to isolate the effects of growth hormone in this complex and poorly understood disease. The short term goal of this proposal is to determine the contribution of growth hormone and IGF-1 to the excess insulin resistance and hyperandrogenism in PCOS. This proposal will investigate these effects first in the less complex lean PCOS patients and then in the more common and more severe obese PCOS patients. The overall hypotheses of this proposal are that growth hormone blockade will 1) decrease insulin resistance in lean women with PCOSto a greater extent than in normals; and 2) decrease androgens in lean women with PCOS more than in control women. These effects are expected to be magnified in obese women with PCOS in comparison to lean women with PCOS. In all groups growth hormone activity will first be blocked at a submaximal level to preserve normal IGF-1 levels, and then at a high level to induce IGF-1 deficiency in order to distinguish between the roles of growth hormone and IGF-1 in PCOS. In addition to the mentored research, the candidate will undertake advanced training in obesity research techniques and biostatistics that will allow her to solidify her foundation in clinical research. This application benefits from the robust, research-intensive environment and resources provided by the Divisions of Endocrinology and Reproductive Endocrinology and the General Clinical Research Center at UNC. The combination of protected time for mentored research and didactic training are ideal and will allow her to develop the experience, skills and preliminary data to develop as an independent clinician- scientist. [unreadable] [unreadable] [unreadable]