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

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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

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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  1. Thomas, J. L., Myers, R. P. & Strickler, R. C. Human placental 3β-hydroxy-5-ene-steroid dehydrogenase and steroid 5/4-ene-isomerase: purification from mitochondria and kinetic profiles, biophysical characterization of the purified mitochondrial and microsomal enzymes. J. Steroid Biochem. 33, 209–217 (1989). · DOI · Paper page
  2. Fluck, C. E., Miller, W. L. & Auchus, R. J. The 17,20-lyase activity of cytochrome p450c17 from human fetal testis favors the Δ5 steroidogenic pathway. J. Clin. Endocrinol. Metab. 88, 3762–3766 (2003). · DOI · Paper page

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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
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
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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