Jun 9, 2009 - Reproductive Biology, Case Western Reserve University School of Medicine, ... We have shown that mononuclear cells (MNC) are pre-activated in .... Department of Pharmacy ... Children's Hospital of Pittsburgh of UPMC,.
ANDROGEN EXCESS & POLYCYSTIC OVARY SYNDROME SOCIETY
7TH ANNUAL MEETING JUNE 9, 2009 Washington, DC, USA
INSULIN SENSITIVITY AND HYPERANDROGENISM IN POLYCYSTIC OVARY SYNDROME ARE RELATED TO INCREASED LIPOPOLYSACCHARIDE-STIMULATED TNFα RELEASE FROM MONONUCLEAR CELLS Frank González(1), Neal S. Rote(2), Judi Minium(2) and John. P. Kirwan(3). (1)Dept. of Obstetrics and Gynecology, Mayo Clinic College of Medicine, Rochester, MN, USA; (2) Dept. of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; (3) Depts. of Gastroenterology and PathoBiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA We have shown that mononuclear cells (MNC) are pre-activated in Polycystic Ovary Syndrome (PCOS), as evidenced by upregulation of proinflammatory molecular pathways that promote insulin resistance and atherogenesis. To confirm this, we examined the effect of in vitro exposure to lipopolysaccharide (LPS) on TNFα release from resting MNC of women with PCOS compared to those of ovulatory controls, and the relationship of this effect with insulin sensitivity, LH and androgens. Fourteen women with PCOS (6 lean, 6 obese) between ages 18-40, diagnosed on the basis of oligo- or amenorrhea and hyperandrogenemia, and 12 ovulatory controls (7 lean, 7 obese) of similar age and body weight were selected for study. Subjects with diabetes, inflammatory illnesses or other endocrinopathies were excluded. TNFα release was measured by ELISA from MNC cultured in the presence and absence of LPS following isolation from fasting blood samples obtained within 5-8 days of menses. Levels of LH, testosterone and androstenedione were measured in serum by RIA. Insulin sensitivity was derived by ISOGTT. ISOGTT was lower in lean and obese women with PCOS compared to lean controls (4.0±0.4 and 2.7±0.7 vs. 7.0±1.3, p
