The overall goal of Dr. Ehrmanns research program is to determine how allelic variation in diabetes susceptibility genes affects glucose tolerance in women with PCOS. Several novel approaches have been developed and are currently being used to test the hypotheses that: 1) glucose tolerance, insulin secretion and insulin action in PCOS are significantly affected by allelic variation in diabetes susceptibility genes; 2) women with PCOS are less able than controls to compensate with insulin secretion to glucocorticoid induced insulin resistance and the inadequate insulin secretory response in PCOS is genetically influenced, and; 3) patterns of gene expression in muscle and fat in response to administration of dexamethasone and/or pioglitazone differ between women with PCOS and controls. Physiologic information collected is used to understand how genetic variation at genes established as risk factors for type 2 diabetes increases risk for PCOS, including characterization of aberrations in -cell function as well as insulin resistance.