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Journal of the Society for Gynecologic Investigation, Vol. 8, No. 1 suppl, S26-S29 (2001)
DOI: 10.1177/107155760100800109
© 2001 SAGE Publications

Insulin-like Growth Factor Family in Graafian Follicle Development and Function

Linda C. Giudice, MD, PhD

Division of Reproductive Endocrinology and Infertility, Center for Research on Women's Health and Reproductive Medicine, Department of Gynecology and Obstetrics, Stanford University Medical Center, Stanford, CA 94305-5317; giudice{at}stanford.edu

The insulin-like growth factor (IGF) family plays an important role in follicle development, dominant follicle growth and steroidogenesis, and follicular atresia. Insulin-like growth factor (IGF)-II is the primary IGF in human ovary, acting as a mediator of gonadotropin action. IGF-II stimulates granulosa steroidogenesis, and its actions, along with those of follicle-stimulating hormone (FSH), are inhibited by IGF binding protein (IGFBP)-4. At the time of follicle selection, in the estrogen-dominant follicle, granulosa IGF-II synthesis increased dramatically. Simultaneously, in the selected follicle, IGFBP-4, an inhibitor of IGF-II action and abundant within androgen-dominant follicles, is proteolyzed by a specific IGFBP-4 protease, resulting in decreased affinity of IGFBP-4 for IGF-II. The IGFBP-4 protease has recently been identified in human ovary as pregnancy-associated plasma protein-A (PAPP-A). In the Graafian follicle, IGF-II bioavailability is increased to act as a mediator of FSH action, by increased synthesis of this peptide and concomitant decrease in an inhibitor of its actions by proteolysis of IGFBP-4.

Key Words: IGF • IGF binding protein • IGF BP protease • pregnancy-associated plasma protein-A


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