title: Hyperandrogenism sensitizes leukocytes to hyperglycemia to promote oxidative stress in lean reproductive-age women.
abstract: BACKGROUND
  Hyperandrogenism and oxidative stress are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate oxidative stress.
  
  
  OBJECTIVE
  The purpose of this study was to determine the effect of oral androgen administration on fasting and glucose-stimulated leukocytic reactive oxygen species (ROS) generation, reduced nicotinamide adenine dinucleotide phosphate oxidase p47(phox) subunit gene expression, and plasma thiobarbituric acid-reactive substances (TBARS) in lean healthy reproductive-age women.
  
  
  METHODS
  Sixteen lean healthy ovulatory reproductive-age women were treated with 130 mg dehydroepiandrosterone (DHEA) or placebo (n = 8 each) for 5 d in this randomized, controlled, double-blind study that was performed at an an academic medical center.
  
  
  METHODS
  Leukocytic ROS generation, p47(phox) gene expression, and plasma TBARS were quantified in the fasting state and 2 h after glucose ingestion, before and after treatment.
  
  
  RESULTS
  Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens or any prooxidant markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-sulfate, increased the percent change in glucose-challenged p47(phox) RNA content, and increased the percent change in fasting and glucose-challenged ROS generation from mononuclear cells and polymorphonuclear cells, p47(phox) protein content, and plasma TBARS.
  
  
  CONCLUSIONS
  Elevation of circulating androgens comparable to what is present in PCOS increases leukocytic ROS generation, p47(phox) gene expression, and plasma TBARS to promote oxidative stress in lean healthy reproductive-age women. Thus, hyperandrogenemia activates and sensitizes leukocytes to glucose in this population.
authors.affiliation: Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. gonzalef@iupui.edu
authors.forename: Frank
authors.initials: F
authors.lastname: González
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
authors.forename: Janice K
authors.initials: JK
authors.lastname: Daniels
authors.forename: Eati
authors.initials: E
authors.lastname: Basal
authors.forename: Jill M
authors.initials: JM
authors.lastname: Schimke
authors.forename: Hilary E
authors.initials: HE
authors.lastname: Blair
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D019255:NADPH Oxidases / Q000235:genetics; D018384:Oxidative Stress; D011085:Polycystic Ovary Syndrome / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D001786:Blood Glucose; D017382:Reactive Oxygen Species; D013739:Testosterone; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1