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The Insulin-Related Ovarian Regulatory System in Health and Disease

Division of Endocrinology, Department of Medicine (L.P.) and Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology (Z.R.), New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, New York 10021; and Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University Medical Center (N.A.C., L.C.G.), Stanford, California 94305

I. Introduction

II. Insulin and Insulin Receptor

A. Structures of insulin and insulin receptor

B. Presence of insulin and insulin receptor in the ovary

C. Insulin action and the ovary

D. Summary

III. IGFs and Their Receptors

A. IGF peptides and receptors

B. Expression of IGFs and IGF receptors in the ovary

C. Role of IGFs in ovulatory function and steroidogenesis

D. Summary

IV. IGF-Binding Proteins (IGFBPs) and Proteases

A. Structural relationships among IGFBPs

B. IGFBP expression in the ovary

C. IGFBP proteases in the ovary

D. IGFBP actions in the ovary

E. Role of IGFBPs in follicular development and atresia

F. Summary

V. Polycystic Ovary Syndrome (PCOS)

A. Clinical features

B. Theories of pathogenesis

C. Insulin resistance in PCOS

D. Alterations of IGFs and IGFBPs in PCOS

E. Summary

VI. The Insulin-Related Ovarian Regulatory System: Implications for Therapy

A. Treatment of PCOS

B. Therapeutic use of IGF-I and IGF-II

C. Use of GH in ovulation induction

VII. Summary and Conclusions