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Increased Activation of Nuclear Factor B Triggers Inflammation and Insulin Resistance in Polycystic Ovary Syndrome

Department of Reproductive Biology (F.G., N.S.R., J.M.), Department of Medicine and Schwartz Center for Metabolism and Nutrition (J.P.K.), Case Western Reserve University School of Medicine, Cleveland, Ohio 44109

Address all correspondence and requests for reprints to: Frank González, MetroHealth Medical Center, Department of Obstetrics and Gynecology, Hamann S4-44, 2500 MetroHealth Drive, Cleveland, Ohio 44109. E-mail: fgonzalez{at}metrohealth.org.

Context: Insulin resistance and chronic low level inflammation are often present in women with polycystic ovary syndrome (PCOS).

Objective: The purpose of this study was to determine the effects of hyperglycemia on nuclear factor B (NFB) activation and inhibitory B (IB) from mononuclear cells (MNC) in PCOS.

Design and Setting: This was a prospective controlled study conducted at an academic medical center.

Patients: The study population consisted of 16 reproductive-age women with PCOS (eight lean, eight obese) and 16 age- and body composition-matched controls (eight lean, eight obese).

Main Outcome Measures: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (IS_OGTT). Intranuclear NFB and IB protein expression were quantitated from MNC obtained from blood drawn fasting and 2 h after glucose ingestion.

Results: IS_OGTT was lower in PCOS compared with controls (3.3 ± 0.3 vs. 6.4 ± 0.9, P < 0.004). The percent change in intranuclear NFB was higher in lean and obese PCOS compared with lean controls (42.5 ± 19.1 and 54.5 ± 12.5 vs. –14.1 ± 10.9, P < 0.006). The percent change in intranuclear NFB correlated positively with 2-h post-glucose ingestion levels (r = 0.37; P < 0.04) and plasma testosterone (r = 0.49; P < 0.006) and correlated negatively with IS_OGTT (r = 0.39; P < 0.04). The percent change in IB was lower in lean and obese PCOS compared with lean controls (–22.3 ± 3.2 and –17.0 ± 5.0 vs. 8.4 ± 11.8, P < 0.02).

Conclusion: In response to hyperglycemia, intranuclear NFB increases and IB decreases in MNC of women with PCOS independent of obesity. This may represent a cardinal inflammatory signal that contributes to the induction of insulin resistance and hyperandrogenism in PCOS.

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