Evidence for Increased 5α-Reductase Activity During Early Childhood in Daughters of Women With Polycystic Ovary Syndrome.

J Clin Endocrinol Metab 2016 05 18;101(5):2069-75. Epub 2016 Mar 18.

Division of Endocrinology, Metabolism, and Molecular Medicine (A.D.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611; Division of Pediatric Endocrinology (L.C.T., N.R.F.), Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611; Institute of Metabolism and Systems Research (J.I., D.M.O., C.H.L.S., W.A.), University of Birmingham, Birmingham B15 2TT, UK; Centre for Endocrinology, Diabetes and Metabolism (J.I., W.A.), Birmingham Health Partners, Birmingham B15 2TT, UK.

Context: Polycystic ovary syndrome (PCOS) is a heritable, complex genetic disease. Animal models suggest that androgen exposure at critical developmental stages contributes to disease pathogenesis. We hypothesized that genetic variation resulting in increased androgen production produces the phenotypic features of PCOS by programming during critical developmental periods. Although we have not found evidence for increased in utero androgen levels in cord blood in the daughters of women with PCOS (PCOS-d), target tissue androgen production may be amplified by increased 5α-reductase activity analogous to findings in adult affected women. It is possible to noninvasively test this hypothesis by examining urinary steroid metabolites.

Objective: We performed this study to investigate whether PCOS-d have altered androgen metabolism during early childhood.

Design, Setting, And Participants: Twenty-one PCOS-d, 1-3 years old, and 36 control girls of comparable age were studied at an academic medical center.

Main Outcome Measures: Urinary steroid metabolites were measured by gas chromatography/mass spectrometry. Twenty-four hour steroid excretion rates and precursor to product ratios suggestive of 5α-reductase and 11β-hydroxysteroid dehydrogenase activities were calculated.

Results: Age did not differ but weight for length Z-scores were higher in PCOS-d compared to control girls (P = .02). PCOS-d had increased 5α-tetrahydrocortisol:tetrahydrocortisol ratios (P = .04), suggesting increased global 5α-reductase activity. There was no evidence for differences in 11β-hydroxysteroid dehydrogenase activity. Steroid metabolite excretion was not correlated with weight.

Conclusions: Our findings suggest that differences in androgen metabolism are present in early childhood in PCOS-d. Increased 5α-reductase activity could contribute to the development of PCOS by amplifying target tissue androgen action.

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Source
http://dx.doi.org/10.1210/jc.2015-3926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870855PMC
May 2016
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