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11-Oxygenated androgens in health and disease
Open accessAbstract
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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“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]
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“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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Metadata
- Authors
- Turcu, A. F., Rege, J., Auchus, R. J., & Rainey, W. E.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Turcu, Adina F.
- Venue
- Nature Reviews Endocrinology
- Published
- 2020-03-16
- Volume
- 16
- Issue
- 5
- Pages
- 284-296
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- 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
- 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
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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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