11β-Hydroxyandrostenedione: downstream metabolism by 11βHSD, 17βHSD and SRD5A produces novel substrates in familiar pathways
Abstract
11β-Hydroxyandrostenedione (11OHA4), a major C19 steroid produced by the adrenal, was first reported in the 1950s. Initially the subject of numerous studies, interest dwindled due to the apparent lack of physiological function and, by the end of the century, 11OHA4 was no longer considered as an adrenal C19 steroid. Our recent studies, however, showed that 11OHA4 is the precursor to novel active androgens which include 11-ketodihydrotestosterone (11KDHT) which has been implicated in prostate cancer, thereby renewing interest in 11OHA4. In this paper we review the biosynthesis and downstream metabolism of 11OHA4. We discuss the extra-adrenal biosynthesis of 11OHA4 in humans and in other species, highlighting the well-documented role of 11OHA4 in the testes of male fish in which the steroid functions as an active androgen. Finally, we discuss the physiological relevance of 11OHA4 metabolism in castration resistant prostate cancer and outline future prospects.
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In women with 21OHD, 11KT rises roughly proportionately to testosterone, reflecting the adrenal rather than gonadal origin of these androgens.
“In women with 21OHD, 11KT rises roughly proportionately to testosterone (123), reflecting the adrenal rather than gonadal origin of these androgens.”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [123]
In contrast, 11KT is inversely proportional to testosterone in men and in boys Tanner stage 3-5 with 21OHD.
“In contrast, 11KT is inversely proportional to testosterone in men (123) and in boys Tanner stage 3-5 (129) with 21OHD.”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [123]
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References 100 · Cited by 68
- Authors
- Swart, A. C., & Storbeck, K.-H.
- Affiliations
- Stellenbosch University (ZA)
- Corresponding author
- Swart, Amanda C.
- Storbeck, Karl-Heinz
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 408
- Pages
- 114-123
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2037689455
- Cited by
- 68
- References
- 100
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 14 · 2018: 3 · 2017: 8 · 2016: 9 · 2015: 2
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- South African National Research Foundation
- South African Medical Research Council
- The Cancer Association of South Africa
- University of Stellenbosch
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Keywords
- 11β-hydroxyandrostenedione, C19 steroids, adrenal steroidogenesis, 11β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, androgen production, castration-resistant prostate cancer, androgen metabolism
- MeSH terms
- Androgens, Androstenedione, Animals, Humans, Membrane Proteins, Substrate Specificity, 17-Hydroxysteroid Dehydrogenases, 11-beta-Hydroxysteroid Dehydrogenases
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