Hyperandrogenism sensitizes leukocytes to hyperglycemia to promote oxidative stress in lean reproductive-age women

Frank González, K. Sreekumaran Nair, Janice K. Daniels, Eati Basal, Jill M. Schimke, Hilary E. Blair

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Context: 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 p47phox subunit gene expression, and plasma thiobarbituric acid-reactive substances (TBARS) in lean healthy reproductive-age women. Participants, Design, and Setting: 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. Main Outcome Measures: 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 p47phox RNA content, and increased the percent change in fasting and glucose-challenged ROS generation from mononuclear cells and polymorphonuclear cells, p47phox protein content, and plasma TBARS. Conclusion: Elevation of circulating androgens comparable to what is present in PCOS increases leukocytic ROS generation, p47phox 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.

Original languageEnglish (US)
Pages (from-to)2836-2843
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number8
DOIs
StatePublished - Aug 1 2012

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Hyperandrogenism
Oxidative stress
Hyperglycemia
Oxidative Stress
Leukocytes
Thiobarbituric Acid Reactive Substances
Glucose
Dehydroepiandrosterone
Fasting
Reactive Oxygen Species
Gene expression
Androgens
Polycystic Ovary Syndrome
Placebos
Plasmas
Gene Expression
Eating
Dehydroepiandrosterone Sulfate
Androstenedione
NADP

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Hyperandrogenism sensitizes leukocytes to hyperglycemia to promote oxidative stress in lean reproductive-age women. / González, Frank; Nair, K. Sreekumaran; Daniels, Janice K.; Basal, Eati; Schimke, Jill M.; Blair, Hilary E.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 8, 01.08.2012, p. 2836-2843.

Research output: Contribution to journalArticle

González, Frank ; Nair, K. Sreekumaran ; Daniels, Janice K. ; Basal, Eati ; Schimke, Jill M. ; Blair, Hilary E. / Hyperandrogenism sensitizes leukocytes to hyperglycemia to promote oxidative stress in lean reproductive-age women. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 8. pp. 2836-2843.
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AB - Context: 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 p47phox subunit gene expression, and plasma thiobarbituric acid-reactive substances (TBARS) in lean healthy reproductive-age women. Participants, Design, and Setting: 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. Main Outcome Measures: 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 p47phox RNA content, and increased the percent change in fasting and glucose-challenged ROS generation from mononuclear cells and polymorphonuclear cells, p47phox protein content, and plasma TBARS. Conclusion: Elevation of circulating androgens comparable to what is present in PCOS increases leukocytic ROS generation, p47phox 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.

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