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This version published online on May 8, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-2846
A more recent version of this article appeared on July 1, 2007
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Submitted on December 21, 2006
Accepted on April 30, 2007

Insulin and IGF stimulation of VEGF production by luteinized granulosa cells: comparison between PCOS and non-PCOS women

Meghan B. Stanek, Sherri M. Borman, Theodore A. Molskness, Janine M. Larson, Richard L. Stouffer, and Phillip E. Patton*

Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon 97239; Division of Reproductive Sciences, Oregon National Primate Research Center, Beaverton, Oregon 97006

* To whom correspondence should be addressed. E-mail: pattonp{at}ohsu.edu.

Context: Vascular endothelial growth factor (VEGF-A) is a potent cytokine that promotes angiogenesis and vascular permeability. Following controlled ovarian hyperstimulation (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 insulin-like growth factors (IGF's) on VEGF-A production by luteinized granulosa cells (LGC's) from women with and without PCOS

Design: A prospective comparative experimental study

Setting: Institutional Practice

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

Interventions: COS for IVF

Main Outcome Measures: VEGF-A levels in culture media collected daily for 3 days from LGC's following incubation with variable doses of insulin, IGF-1, IGF-2, 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's increased VEGF-A levels within 1 day and appeared to synergize with LH at 3 days. VEGF-A production by non-PCOS LGC's 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 to non-PCOS LGC's.

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


Key words: PCOS • VEGF-A • insulin • IGF




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