title: Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome.
abstract: BACKGROUND
  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 reactive oxygen species (ROS) generation from mononuclear cells (MNCs) in PCOS.
  
  
  METHODS
  This was a prospective controlled study.
  
  
  METHODS
  The study was conducted at an academic medical center.
  
  
  METHODS
  The study population consisted of 16 women with PCOS (eight lean, eight obese) and 15 age- and body composition-matched controls (eight lean, seven obese).
  
  
  METHODS
  Insulin sensitivity was derived from a 2-h, 75-g oral glucose tolerance test (IS(OGTT)). ROS generation and p47(phox) protein expression were quantitated from MNCs obtained from blood drawn fasting and 2 h after glucose ingestion.
  
  
  RESULTS
  IS(OGTT) was lower in PCOS, compared with controls (3.1 +/- 0.3 vs. 6.3 +/- 0.9, P < 0.003). The percent change in ROS generation from MNCs was higher in lean and obese PCOS, compared with lean controls (138.8 +/- 21.3 and 154.2 +/- 49.1 vs. 0.6 +/- 12.7, P < 0.003). The percent change in ROS generation from MNCs correlated positively with glucose area under the curve (r = 0.38, P < 0.05), and plasma levels of testosterone (r = 0.59, P < 0.002) and androstenedione (r = 0.50, P < 0.009). The percent change in p47(phox) from MNCs was also higher in lean and obese PCOS, compared with lean controls (36.2 +/- 18.2 and 39.1 +/- 8.0 vs. -13.7 +/- 8.7, P < 0.02), and correlated negatively with IS(OGTT) (r = -0.39, P < 0.05).
  
  
  CONCLUSIONS
  ROS generation from MNCs in response to hyperglycemia is increased in PCOS independent of obesity. The resultant oxidative stress may contribute to a proinflammatory state that induces insulin resistance and hyperandrogenism in women with this disorder.
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109, USA. fgonzalez@metrohealth.org
authors.forename: Frank
authors.initials: F
authors.lastname: González
authors.forename: Neal S
authors.initials: NS
authors.lastname: Rote
authors.forename: Judi
authors.initials: J
authors.lastname: Minium
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
mesh_terms: D000328:Adult; D000735:Androstenedione / Q000097:blood; D019540:Area Under Curve; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D017588:Hyperandrogenism / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D015227:Lipid Peroxidation / Q000187:drug effects; D009000:Monocytes / Q000378:metabolism; D019255:NADPH Oxidases; D009765:Obesity / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D017382:Reactive Oxygen Species; D013739:Testosterone / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D049629:Waist-Hip Ratio
chemical_list: D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D013739:Testosterone; D000735:Androstenedione; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D005947:Glucose