INSULIN ACTION IN THE POLYCYSTIC OVARY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5-10% of this population. It is the leading cause of hormonally-related infertility. Women with PCOS have elevated male hormone levels and irregular periods. They frequently have insulin resistance, conferring a seven-fold increased risk for type 2 diabetes mellitus (adult onset). PCOS is an inherited disorder. We recently discovered a genetic marker, allele 8 (A8) of D19S884, which is located on chromosome 19 near the insulin receptor. This marker is significantly associated with the PCOS reproductive phenotype. Androgen, insulin, glucose and lipid levels will be measured in all subjects. Intensive testing to examine the metabolic and lipid abnormalities associated with PCOS will be performed. Differences in insulin secretion and action, obesity risk, and metabolic response to over- and underfeeding will be compared in A8+ and A8- PCOS women as well as controls. A8+ male first-degree male relatives of PCOS women will be examined to see if they have similar metabolic alterations identified in A8+ PCOS women. Small samples of abdominal fat obtained by aspiration and mid-thigh muscle obtained by biopsy will be examined in in vitro studies of insulin sensitivity.