title: Induction of hyperandrogenism in lean reproductive-age women stimulates proatherogenic inflammation.
abstract: We determined the effect of hyperandrogenemia as observed in polycystic ovary syndrome (PCOS) on fasting and glucose-stimulated proatherogenic inflammation markers in lean healthy reproductive-age women. Sixteen lean healthy ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo (n=8 each) for 5 days. Interleukin-6 (IL-6) mRNA and IL-6 release from mononuclear cells (MNC), plasma IL-6 and C-reactive protein (CRP), and MNC-derived (matrix metalloproteinase-2) MMP-2 protein were quantified in the fasting state and 2 h after glucose ingestion, before and after treatment. Before treatment, subjects receiving dehydroepinadrosterone (DHEA) or placebo exhibited no differences in androgens, or any proatherogenic inflammation markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-sulfate (DHEA-S), and increased the percent change from baseline in fasting IL-6 mRNA, IL-6 release, plasma IL-6, and CRP and MMP-2 protein. However, there were no differences in any of the proatherogenic inflammation markers following glucose ingestion after DHEA administration. We conclude that in lean reproductive-age women, proatherogenic inflammation in the fasting state increases after raising circulating androgens to levels observed in PCOS. However, this hyperandrogenemia-induced MNC activation does not provoke a similar response to subsequent glucose ingestion.
authors.affiliation: Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: F
authors.initials: F
authors.lastname: González
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: K
authors.initials: K
authors.lastname: Sreekumaran Nair
authors.affiliation: Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: E
authors.initials: E
authors.lastname: Basal
authors.affiliation: Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Bearson
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Schimke
authors.affiliation: Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: H E
authors.initials: HE
authors.lastname: Blair
mesh_terms: D000328:Adult; D000728:Androgens / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003687:Dehydroepiandrosterone; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000097:blood* / Q000139:chemically induced; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D011085:Polycystic Ovary Syndrome / Q000097:blood; D055815:Young Adult
chemical_list: D000728:Androgens; C508600:IL6 protein, human; D015850:Interleukin-6; D003687:Dehydroepiandrosterone; D002097:C-Reactive Protein; D020778:Matrix Metalloproteinase 2