The Insulin-Related Ovarian Regulatory System in Health and Disease

INSULIN, a pancreatic peptide hormone produced in the β-cells of the islets of Langerhans, plays a major role in the regulation of carbohydrate, fat, and protein metabolism (1). The classical target organs for insulin action are muscle, adipose tissue, and liver (2). Until approximately a decade ago, insulin was not thought to play a significant role in the regulation of ovarian function, despite suggestions of the “gonadotropic” function of insulin (3) in observations of abnormal ovarian function in young women with type 1 diabetes mellitus by Joslin et al. (4), which predated the discovery of insulin more than 75 years ago (5). A resurgence of interest in the ovarian effects of insulin was stimulated by observations of severe ovarian hyperandrogenism in women with syndromes of extreme insulin resistance (6, 7), which led to the hypothesis that high levels of circulating insulin may cause excessive androgen production in these patients (8, 9). The demonstration of insulin’s ability to stimulate steroidogenesis in ovarian cells in vitro (10) and the demonstration of insulin receptors in both stromal and follicular compartments of the human ovary (11, 12) established the ovary as another important target organ for insulin action.