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Journal of Endocrinology (2006) 188, 521-529       DOI: 10.1677/joe.1.06579
© 2006 Society for Endocrinology
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In vitro evidence that hyperglycemia stimulates tumor necrosis factor-{alpha} release in obese women with polycystic ovary syndrome

F González1, N S Rote1, J Minium1 and J P Kirwan2

1 Department of Reproductive Biology and
2 Department of Medicine, Schwartz Center for Metabolism and Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109, USA

(Requests for offprints should be addressed to F González, MetroHealth Medical Center, Department of Obstetrics and Gynecology, Hamann S4-44, 2500 MetroHealth Drive, Cleveland, Ohio 44109, USA; Email: fgonzalez{at}metrohealth.org)

Women with polycystic ovary syndrome (PCOS) are often insulin resistant and have chronic low-level inflammation. The purpose of this study was to determine the effects of hyperglycemia in vitro on tumor necrosis factor (TNF)-{alpha} release from mononuclear cells (MNC) in PCOS. Twelve reproductive-age women with PCOS (six lean, six obese) and 12 age-matched controls (six lean, six obese) were studied. Insulin sensitivity (ISHOMA) was estimated from fasting levels of glucose and insulin and percent truncal fat was determined by dual energy absorptiometry (DEXA). TNF{alpha} release was measured from MNC cultured under euglycemic and hyperglycemic conditions. ISHOMA was higher in obese women with PCOS than in lean women with PCOS (student’s t-test; 73.7 ± 14.8 vs 43.1 ± 8.6, P < 0.05), but similar to that of obese controls. ISHOMA was positively correlated with percent truncal fat (r=0.57, P < 0.04). Obese women with PCOS exhibited an increase in the percent change in TNF{alpha} release from MNC in response to hyperglycemia compared with obese controls (10 mM, 649 ± 208% vs 133 ± 30%, P < 0.003; 15 mM, 799 ± 347% vs 183 ± 59%, P < 0.04). The TNF{alpha} response directly correlated with percent truncal fat (r=0.45, P < 0.03) and ISHOMA (r=0.40, P < 0.05) for the combined groups, and with plasma testosterone (r=0.60, P < 0.05) for women with PCOS. MNC of obese women with PCOS exhibit an increased TNF{alpha} response to in vitro physiologic hyperglycemia. MNC-derived TNF{alpha} release may contribute to insulin resistance and hyperandrogenism, particularly when the combination of PCOS and increased adiposity is present.




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