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

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Evidence for Increased 5α-Reductase Activity During Early Childhood in Daughters of Women with Polycystic Ovary Syndrome. / Arlt, Wiebke; Torchen, Laura; Idkowiak, Jan; Fogel, Naomi; O'Neil, Donna; Shackleton, Cedric; Dunaif, Andrea.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 5, 05.2016, p. 2069-2075.

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@article{46d367aa62d741abb7508827f9e924af,
title = "Evidence for Increased 5α-Reductase Activity During Early Childhood in Daughters of Women with Polycystic Ovary Syndrome",
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.",
keywords = "Journal Article",
author = "Wiebke Arlt and Laura Torchen and Jan Idkowiak and Naomi Fogel and Donna O'Neil and Cedric Shackleton and Andrea Dunaif",
year = "2016",
month = may,
doi = "10.1210/jc.2015-3926#sthash.9Wp6MrQ4.dpuf",
language = "English",
volume = "101",
pages = "2069--2075",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Endocrine Society",
number = "5",

}

RIS

TY - JOUR

T1 - Evidence for Increased 5α-Reductase Activity During Early Childhood in Daughters of Women with Polycystic Ovary Syndrome

AU - Arlt, Wiebke

AU - Torchen, Laura

AU - Idkowiak, Jan

AU - Fogel, Naomi

AU - O'Neil, Donna

AU - Shackleton, Cedric

AU - Dunaif, Andrea

PY - 2016/5

Y1 - 2016/5

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1210/jc.2015-3926#sthash.9Wp6MrQ4.dpuf

DO - 10.1210/jc.2015-3926#sthash.9Wp6MrQ4.dpuf

M3 - Article

C2 - 26990942

VL - 101

SP - 2069

EP - 2075

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 5

ER -