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Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women.

ABSTRACT: Hyperandrogenism and chronic low-grade inflammation are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate inflammation. We determined the effect of oral androgen administration on fasting and glucose-stimulated nuclear factor-?B (NF-?B) activation and expression and related markers of inflammation in mononuclear cells (MNC) of lean reproductive-age women. Sixteen lean, ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo (n = 8 each) for 5 days in a randomized, controlled, double-blind fashion. Nuclear activation of NF-?B, p65 and p105 NF-?B subunit RNA, TNF? and IL-1? mRNA, and NF-?B p65 and inhibitory-?B (I?B) protein were quantified from MNC obtained while fasting and 2 h after glucose ingestion, before and after DHEA or placebo administration. Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens or any inflammatory markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-S, increased the percent change in fasting and glucose-challenged activated NF-?B, p65, p105, TNF?, and IL-1? RNA and p65 protein, and decreased the percent change in fasting and glucose-challenged I?B protein. We conclude that elevation of circulating androgens to the range observed in PCOS upregulates the NF-?B inflammation pathway in lean reproductive-age women. Thus, hyperandrogenemia activates and sensitizes MNC to glucose in this population.

SUBMITTER: Gonzalez F

PROVIDER: S-EPMC3287360 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women.

González Frank F Nair K Sreekumaran KS Daniels Janice K JK Basal Eati E Schimke Jill M JM

American journal of physiology. Endocrinology and metabolism 20111101 3

Hyperandrogenism and chronic low-grade inflammation are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate inflammation. We determined the effect of oral androgen administration on fasting and glucose-stimulated nuclear factor-κB (NF-κB) activation and expression and related markers of inflammation in mononuclear cells (MNC) of lean reproductive-age women. Sixteen lean, ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo ...[more]

PMID: 22045316

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Project description:Potentially teratogenic medications are frequently prescribed without provision of contraceptive counseling.To evaluate whether computerized clinical decision support (CDS) can increase primary care providers' (PCPs') provision of family planning services when prescribing potentially teratogenic medications.Cluster-randomized trial conducted in one academic and one community-based practice between October of 2008 and April of 2010.Forty-one PCPs were randomized to receive one of two types of CDS which alerted them to risks of medication-induced birth defects when ordering potentially teratogenic medications for women who may become pregnant. The 'simple' CDS provided a cautionary alert; the 'multifaceted' CDS provided tailored information and links to a structured order set designed to facilitate safe prescribing. Both CDS systems alerted PCPs about medication risk only once per encounter.We assessed change in documented provision of family planning services using data from 35,110 encounters and mixed-effects models. PCPs completed surveys before and after the CDS systems were implemented, allowing assessment of change in PCP-reported counseling about the risks of medication-induced birth defects and contraception.Both CDS systems were associated with slight increases in provision of family planning services when potential teratogens were prescribed, without a significant difference in improvement by CDS complexity (p = 0.87). Because CDS was not repeated, 13% of the times that PCPs received CDS they substituted another potential teratogen. PCPs reported significant improvements in several counseling and prescribing practices. The multifaceted group reported a greater increase in the number of times per month they discussed the risks of medication use during pregnancy (multifaceted: +4.9 ± 7.0 vs. simple: +0.8 ± 3.2, p = 0.03). The simple CDS system was associated with greater clinician satisfaction.CDS systems hold promise for increasing provision of family planning services when fertile women are prescribed potentially teratogenic medications, but further refinement of these systems is needed.

Dataset Information

Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women.

Publications

Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women.

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