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Sex hormones and gene expression signatures in peripheral blood from postmenopausal women - the NOWAC postgenome study.

ABSTRACT: BACKGROUND: Postmenopausal hormone therapy (HT) influences endogenous hormone concentrations and increases the risk of breast cancer. Gene expression profiling may reveal the mechanisms behind this relationship.Our objective was to explore potential associations between sex hormones and gene expression in whole blood from a population-based, random sample of postmenopausal women METHODS: Gene expression, as measured by the Applied Biosystems microarray platform, was compared between hormone therapy (HT) users and non-users and between high and low hormone plasma concentrations using both gene-wise analysis and gene set analysis. Gene sets found to be associated with HT use were further analysed for enrichment in functional clusters and network predictions. The gene expression matrix included 285 samples and 16185 probes and was adjusted for significant technical variables. RESULTS: Gene-wise analysis revealed several genes significantly associated with different types of HT use. The functional cluster analyses provided limited information on these genes. Gene set analysis revealed 22 gene sets that were enriched between high and low estradiol concentration (HT-users excluded). Among these were seven oestrogen related gene sets, including our gene list associated with systemic estradiol use, which thereby represents a novel oestrogen signature. Seven gene sets were related to immune response. Among the 15 gene sets enriched for progesterone, 11 overlapped with estradiol. No significant gene expression patterns were found for testosterone, follicle stimulating hormone (FSH) or sex hormone binding globulin (SHBG). CONCLUSIONS: Distinct gene expression patterns associated with sex hormones are detectable in a random group of postmenopausal women, as demonstrated by the finding of a novel oestrogen signature.

SUBMITTER: Waaseth M

PROVIDER: S-EPMC3078834 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Sex hormones and gene expression signatures in peripheral blood from postmenopausal women - the NOWAC postgenome study.

Waaseth Marit M Olsen Karina S KS Rylander Charlotta C Lund Eiliv E Dumeaux Vanessa V

BMC medical genomics 20110331

<h4>Background</h4>Postmenopausal hormone therapy (HT) influences endogenous hormone concentrations and increases the risk of breast cancer. Gene expression profiling may reveal the mechanisms behind this relationship.Our objective was to explore potential associations between sex hormones and gene expression in whole blood from a population-based, random sample of postmenopausal women<h4>Methods</h4>Gene expression, as measured by the Applied Biosystems microarray platform, was compared between ...[more]

PMID: 21453500

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Project description:The aim of the study was to compare the effects of vitamin D3 supplementation versus placebo on serum sex hormones in postmenopausal women completing a 12-month diet + exercise weight loss program.Two hundred eighteen overweight or obese women (50-75 y) with serum 25-hydroxyvitamin D at least 10 to less than 32?ng/mL ("insufficient") were randomized to either weight loss + 2,000?IU/day oral vitamin D3, or to weight loss + daily placebo. Serum sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone were measured by radioimmunoassay before randomization and at 12 months. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations.The 12-month changes in sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone did not differ between groups (all P?>?0.05). However, a greater increase in serum 25-hydroxyvitamin D was associated with a greater increase in sex hormone-binding globulin (Ptrend?=?0.01), and larger decreases in free and bioavailable estradiol (Ptrend?=?0.04, Ptrend?=?0.03, respectively). In post-hoc analyses, we compared women randomized to vitamin D whose serum 25-hydroxyvitamin D remained insufficient (n?=?38), to women who became replete (25-hydroxyvitamin D ?32?ng/mL; n?=?53). Replete women showed greater reductions in bioavailable estradiol (-1.8 vs -0.7?pg/mL), free testosterone (-0.8 vs -0.3?pg/mL), and bioavailable testosterone (-1.8 vs -0.6?ng/dL), and a greater increase in sex hormone-binding globulin (10.6 vs 4.7?nmol/L) (all P?<?0.05), even after adjusting for differences in total 12-month weight loss.Overall, 12-month changes in sex hormone did not differ between groups. However, vitamin D repletion was associated with greater reductions in sex hormones during weight loss, with a possible dose-dependent effect. Future studies should test higher doses and target circulating 25-hydroxyvitamin D levels when measuring such effects.

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Sex hormones and gene expression signatures in peripheral blood from postmenopausal women - the NOWAC postgenome study.

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Sex hormones and gene expression signatures in peripheral blood from postmenopausal women - the NOWAC postgenome study.

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