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Hyperandrogenism induced proinflammatory response to glucose
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Hyperandrogenism induced inflammation that promotes the transcription of tumor necrosis factor-alpha — a known mediator of insulin resistance — in lean and healthy reproductive-aged women, according to researchers.
“These results corroborate our previous reports to bolster the concept that, in [polycystic ovary syndrome], hyperandrogenism may be the progenitor of nutrient-induced inflammation and is independent of obesity or excess abdominal adiposity,” researchers wrote.
The patients (aged 20-40 years) included lean, healthy reproductive-age women who were administered 130 mg dehydroepiandrosterone (DHEA; n=8) or placebo (n=8) for 5 days. Twelve patients also provided untreated fasting blood samples for cell culture experiments, according to researchers.
Androgen receptor mRNA content and tumor necrosis factor (TNF)-alpha release measurements were conducted before and after the administration of DHEA in the fasting state and 2 hours after glucose ingestion, according to data. The researchers also measured the fasting state in cultured mononuclear cell (MNC) exposed to androgens with or without flutamide preincubation to examine the in vivo and in vitro effects of hyperandrogenism on MNC-derived androgen receptor status and TNF-alpha release.
Baseline data indicated that patients administered DHEA or placebo demonstrated no significant differences in androgens and TNF-alpha release from MNC before and after glucose ingestion.
Patients who were administered DHEA exhibited increased levels of testosterone, androstenedione and DHEA-sulfate, and increased MNC-derived androgen receptor mRNA content and TNF-alpha release in the fasting period and in response to glucose ingestion vs. placebo, researchers wrote.
The absolute change in TNF-alpha release increased after testosterone concentrations of 125 ng/dL and 250 ng/dL, and DHEA concentration of 1,750 ng/dL vs. MNC exposure to baseline concentrations of DHEA (175 ng/dL) or testosterone (50 ng/dL). The TNF-alpha response was reduced by preincubation with flutamide (≥60%) across all testosterone concentrations, according to data.
“Further studies are warranted to evaluate whether chronic androgen administration in a large cohort can adequately alter MNC to produce any substantial metabolic abnormalities,” researchers wrote.
Disclosure: The researchers report no relevant financial disclosures.
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