The ovary may not be an obvious target tissue for insulin action but there is ample evidence to suggest that insulin affects glucose metabolism, steroidogenesis and cell growth/differentiation, and that these effects are relevant to both normal ovarian physiology and to disorders of ovarian function. Glucose uptake and glycolysis by granulosa cells - important for providing energy for the maturing oocyte are regulated by both insulin and gonadotrophins. In the human ovary, insulin is equipotent to insulin-like growth factor-1 (IGF-1) in stimulating steroid production by granulosa cells of large antral follicles, and more effective that IGF-1 in stimulating proliferation of ovarian stromal fibroblasts. As in classic target tissues, the diverse effects of insulin in the ovary appear to be mediated by a diversity of post-receptor signaling pathways. Hyperinsulinaemia and insulin resistance are recognized features of polycystic ovary syndrome (PCOS) and there is evidence that augmentation, in granulosa cells, of the action of luteinising hormone (LH) by insulin is implicated in the mechanism of arrested follicle development that is characteristic of anovulation in PCOS. Such an effect of insulin may seem paradoxical, given that there is tissue resistance to the effects of insulin in PCOS, but recent data from our laboratory suggest that insulin resistance in the polycystic ovary selectively affects the metabolic action of insulin on pyruvate production by granulosa cells, a mechanism likely to be mediated by the activity of the phosphotidylinositol 3-kinase (PI3-kinase) pathway.
22 - 24 Mar 2004
British Endocrine Societies