Hyperandrogenism induces a proinflammatory TNF-α response to glucose ingestion in a receptor-dependent fashion

Frank González, Chang Ling Sia, Dawn M. Bearson, Hilary E. Blair

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Context: Hyperandrogenism and inflammation are related in polycystic ovary syndrome (PCOS). Hyperandrogenemia can induce inflammation in reproductive-agewomen,but the mechanism for this phenomenon is unclear. Objective: We examined the in vivo and in vitro effects of hyperandrogenism on mononuclear cell (MNC)-derived androgen receptor (AR) status and TNF release. Design: This study combined a randomized, controlled, double-blind protocol with laboratorybased cell culture experiments. Setting: This work was performed in an academic medical center. Participants: Lean, healthy, reproductive-age women were treated with 130 mg of dehydroepiandrosterone (DHEA) or placebo (n = 8 subjects each) for 5 days and also provided untreated fasting blood samples (n = 12 subjects) for cell culture experiments. Main Outcome Measures: AR mRNA content and TNFα release were measured before and after DHEA administration in the fasting state and 2 hours after glucose ingestion. TNFα release in the fasting state was also measured in cultured MNCs exposed to androgens with or without flutamide preincubation. Results: At baseline, subjects receiving DHEA or placebo exhibited no significant difference in androgens and TNFα release from MNCs before and after glucose ingestion. Compared with placebo, DHEA administration raised levels of T, androstenedione, and DHEA sulfate, and increased MNC-derived AR mRNA content and TNFα release in the fasting state and in response to glucose ingestion. Compared with MNC exposure to baseline concentrations of DHEA (175 ng/dL) or T (50 ng/dL), the absolute change inTNFα release increased after exposure to T concentrations of 125and 250 ng/dL and a DHEA concentration of 1750 ng/dL. Preincubation with flutamide reduced the TNFα response by 60% across all T concentrations. Conclusion: Androgen excess in vivo and in vitro comparable to what is present in PCOS increases TNFα release from MNCs of lean healthy reproductive-age women in a receptor-dependent fashion. Hyperandrogenemia activates and sensitizes MNCs to glucose in this population.

Original languageEnglish (US)
Pages (from-to)E848-E854
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number5
DOIs
StatePublished - May 2014

ASJC Scopus subject areas

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

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