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Insulin and Insulin-Like Growth Factor Stimulation of Vascular Endothelial Growth Factor Production by Luteinized Granulosa Cells: Comparison between Polycystic Ovarian Syndrome (PCOS) and Non-PCOS Women

Department of Obstetrics and Gynecology (M.B.S., J.M.L., P.E.P.), Oregon Health & Science University, Portland, Oregon 97239; and Division of Reproductive Sciences (S.M.B., T.A.M., R.L.S.), Oregon National Primate Research Center, Beaverton, Oregon 97006

Address all correspondence to: Phillip E. Patton, M.D., OHSU Fertility Consultants, Center for Health and Healing, CH10F, 3303 SW Bond Avenue, Portland, Oregon 97239-4501. E-mail: pattonp{at}ohsu.edu.

Context: Vascular endothelial growth factor A (VEGF-A) is a potent cytokine that promotes angiogenesis and vascular permeability. After controlled ovarian stimulation (COS) for in vitro fertilization (IVF), excessive VEGF-A production can occur, particularly in women with polycystic ovarian syndrome (PCOS); however, it is unclear whether the regulation of VEGF-A production is different between PCOS and non-PCOS women.

Objective: The aim of this study was to determine whether there were differences in the dose- and time-dependent effects of insulin and IGFs on VEGF-A production by luteinized granulosa cells (LGCs) from women with and without PCOS.

Design and Setting: A prospective comparative experimental study was conducted at an institutional practice.

Patients: Patients included six PCOS and six non-PCOS women undergoing COS and IVF.

Interventions: Interventions included COS for IVF.

Main Outcome Measures: VEGF-A levels in culture media were collected daily for 3 d from LGCs after incubation with variable doses of insulin, IGF-I, and IGF-II in the presence and absence of LH.

Results: In both study groups, exposure to LH alone did not alter VEGF-A levels. However, insulin or IGF increased VEGF-A levels within 1 d and appeared to synergize with LH at 3 d. VEGF-A production by non-PCOS LGCs was more sensitive to IGF exposure, whereas PCOS cells were more sensitive to insulin. Although an increase in DNA content (P < 0.05) was noted in cultures of PCOS cells, progesterone levels were lower compared with non-PCOS LGCs.

Conclusion: Insulin and IGFs promote VEGF-A production in LGCs, but the response patterns are different when cells from PCOS and non-PCOS women are compared.

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