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Altered Regulation of Insulin-Like Growth Factor Binding Protein-I in Patients With Polycystic Ovary Syndrome

Frank Z. Stanczyk, PhD

Randy S. Morris, MD

Phillip D. K. Lee, MD

Gopal Savjani, MS

Division of Reproducive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California; Cattedra di Endocrinologia, Uiversita di Palermo, Palermo, Italy; Diagnostic Systems Laboratories, Inc., Webster, Texas

Rogerio A. Lobo, MD

Division of Reproducive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California; Cattedra di Endocrinologia, Uiversita di Palermo, Palermo, Italy; Diagnostic Systems Laboratories, Inc., Webster, Texas; Department of Obstetrics and Gynecology, Columbia-Presbyterian Medical Center, 622 West 168th St., PH-16, Room 28E, New York, NY 10032-3784

Objective: Insulin-like growth factor (IGF-I) action is influenced by circulating as well as tissue levels of its binding proteins. Because serum IGF binding protein-1 (IGFBP-1) levels have been found to be decreased in patients with polycystic ovary syndrome (PCOS), we tested the hypothesis that regulation of IGFBP-1 secretion may be different in patients with PCOS compared with normal women.

Methods: We studied 15 normal ovulatory women and 15 women with PCOS of similar age (21 ± 1 and 22 ± 1 years, respectively). All subjects were studied after an overnight fast between days 5-8 after spontaneous or progestin-induced menses. Perturbations included the administration of insulin intravenously, maintenance of a euglycemic clamp, and, in a subsequent cycle, the administration of a long-acting somatostatin analogue (octreotide, 100 µg) given subcutaneously. Blood samples were collected before treatment, every 15 minutes for 6 hours after insulin, and every 30 minutes for 3 hours after octreotide administration. Serum levels of IGF-I, IGFBP-1, IGFBP-3, and insulin were measured by specific immunoassays.

Results: Compared with the controls, patients with PCOS had significantly higher insulin levels, similar IGF-I and IGFBP-3 levels, and significantly lower IGFBP-1. INsulin did not change serum IGF-I levels in either group, although a significant decrease in IGFBP-1 levels occurred in normal women but ot in patients with PCOS. Octreotide treatment also did not change serum IGF-I levels in either group, but serum insulin levels decreased significantly and IGFBP-1 levels increased significantly in both groups; this response was significantly greater in controls.

Conclusion: Our data are compatible with the notion that regulation of IGFBP-1 is altered in women with PCOS and that several factors may be involved.

Key Words: Insulin-like growth factor binding-protein 1 • polycystic ovary syndrome

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