Evidence for increased 5α-reductase activity during early childhood in daughters of women with polycystic ovary syndrome
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
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.
Date Issued
2016-05-01
Date Acceptance
2016-03-14
Citation
Journal of Clinical Endocrinology and Metabolism (JCEM), 2016, 101 (5), pp.2069-2075
ISSN
0021-972X
Publisher
Oxford University Press
Start Page
2069
End Page
2075
Journal / Book Title
Journal of Clinical Endocrinology and Metabolism (JCEM)
Volume
101
Issue
5
Copyright Statement
This article has been published under the terms of the Creative Commons Attribution License(CC-BY;https://creativecommons.org/licenses/by/4.0/),whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsource are credited. Copyright for this article is retained by the author(s)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/26990942
Subjects
ANDROGEN
COMPONENT
Endocrinology & Metabolism
FEMALE RHESUS-MONKEYS
GENOME-WIDE ASSOCIATION
Life Sciences & Biomedicine
METABOLISM
PITUITARY-GONADAL RELATIONS
PUBERTY
Science & Technology
SECRETION
TYPE-1
WEIGHT
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2016-05-01