11-Oxygenated androgens in health and disease

Turcu, Adina F.; Rege, Juilee; Auchus, Richard J.; Rainey, William E.

doi:10.1038/s41574-020-0336-x

Cited by 217Hormonal and reproductive studiesAdrenal Hormones and DisordersSexual Differentiation and Disorders

11-Oxygenated androgens in health and disease

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Turcu, Adina F., Rege, Juilee, Auchus, Richard J., Rainey, William E.·2020·Nature Reviews Endocrinology

DOI 10.1038/s41574-020-0336-xPMC PMC7881526

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Abstract

The adrenal gland is a source of sex steroid precursors, and its activity is particularly relevant during fetal development and adrenarche. Following puberty, the synthesis of androgens by the adrenal gland has been considered of little physiologic importance. Dehydroepiandrosterone (DHEA) and its sulfate, DHEAS, are the major adrenal androgen precursors, but they are biologically inactive. The second most abundant unconjugated androgen produced by the human adrenals is 11β-hydroxyandrostenedione (11OHA4). 11-Ketotestosterone, a downstream metabolite of 11OHA4 (which is mostly produced in peripheral tissues), and its 5α-reduced product, 11-ketodihydrotestosterone, are bioactive androgens, with potencies equivalent to those of testosterone and dihydrotestosterone. These adrenal-derived androgens all share an oxygen atom on carbon 11, so we have collectively termed them 11-oxyandrogens. Over the past decade, these androgens have emerged as major components of several disorders of androgen excess, such as congenital adrenal hyperplasia, premature adrenarche and polycystic ovary syndrome, as well as in androgen-dependent tumours, such as castration-resistant prostate cancer. Moreover, in contrast to the more extensively studied, traditional androgens, circulating concentrations of 11-oxyandrogens do not demonstrate an age-dependent decline. This Review focuses on the rapidly expanding knowledge regarding the implications of 11-oxyandrogens in human physiology and disease.

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Adrenal-specific metabolites such as 21-deoxycortisol and 11-oxygenated androgens may provide more direct evidence for adrenal androgen production in CAH.
“Adrenalspecific metabolites such as 21-deoxycortisol (387) and 11-oxygenated androgens (86) may provide more direct evidence for adrenal androgen production in CAH.”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [86]
11-oxygenated adrenal metabolites are bioactive, dominant steroids in CAH.
“These under-recognized 11-oxygenated adrenal metabolites are bioactive, dominant steroids in CAH15,20,49,50.”
From Management challenges and therapeutic advances in congenital adrenal hyperplasia (2022) · cites this paper as [50]

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8.20 11-Oxygenated androgens in health and disease
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Authors: Turcu, A. F., Rege, J., Auchus, R. J., & Rainey, W. E.
Affiliations: University of Michigan (US)
Corresponding author: Turcu, Adina F.
ORCID: Turcu, Adina F.
Rege, Juilee
Auchus, Richard J.
Rainey, William E.
Venue: Nature Reviews Endocrinology
Publisher: Springer Science and Business Media LLC
Published: 2020-03-16
Volume: 16
Issue: 5
Pages: 284-296
ISSN: 1759-5029 (ISSN-L)
1759-5037
DOI: 10.1038/s41574-020-0336-x
PMC: PMC7881526
OpenAlex: W3010961934
Cited by: 217
References: 230
Citations by year: 2026: 48 · 2025: 39 · 2024: 36 · 2023: 30 · 2022: 29 · 2021: 29 · 2020: 6
FWCI: 3.61
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Reviews Endocrinology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of General Medical Sciences (R01GM086596)
National Institute of Diabetes and Digestive and Kidney Diseases (K08DK109116, R01DK069950, R01DK043140)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
Keywords: adrenal androgens, 11β-hydroxyandrostenedione, 11-ketotestosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, congenital adrenal hyperplasia, premature adrenarche, polycystic ovary syndrome, castration-resistant prostate cancer, adrenal steroidogenesis, fetal development, adrenarche
MeSH terms: Adrenal Glands, Adrenal Hyperplasia, Congenital, Androgens, Endocrine System Diseases, Female, Humans, Male, Oxygen, Polycystic Ovary Syndrome, Prostatic Neoplasms, Puberty, Precocious

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11-Oxygenated androgens in health and disease

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