The role of 5α-reduction in steroid hormone physiology
Abstract
A role for 5alpha-reduction in androgen physiology was first established with the recognition that dihydrotestosterone, the 5alpha-reduced metabolite of testosterone, is formed in many androgen target tissues, binds to the androgen receptor with greater affinity than testosterone, and plays an essential role in virilization of the urogenital sinus and urogenital tubercle during male development. Two 5alpha-reductases perform this reaction, and both isoenzymes utilize NADPH as cofactor and have broad specificity for steroids containing a delta4,3-keto configuration. 5alpha-Reduction, which is essentially irreversible, flattens the steroid molecule because of altered relation of the A and B rings, and stabilizes the hormone-receptor complex. Studies involving in vitro reporter gene assays and intact mice in which both isoenzymes are disrupted, indicate that the fundamental effect of dihydrotestosterone formation is to amplify hormonal signals that can be mediated by testosterone at higher concentrations. 5alpha-Reduction also plays a role in the action of other steroid hormones, including the plant growth hormone, brassinolide, the boar pheromones, androstanol and androstenol, progesterone (in some species), and, possibly, aldosterone and cortisol. The fact that the reaction is important in plants and animals implies a fundamental role in steroid hormone action.
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Testicular testosterone must be converted to DHT at the target organ to induce masculinization.
“testicular testosterone must be converted to DHT at the target organ to induce masculinization [64]”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [64]
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Diseases of the Canine Prostate Gland
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- Authors
- Wilson, J. D.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Wilson, Jean D.
- Venue
- Reproduction Fertility and Development
- Publisher
- CSIRO Publishing
- Published
- 2002-02-13
- Volume
- 13
- Issue
- 8
- Pages
- 673-678
- ISSN
- 1031-3613 (ISSN-L)
- 1448-5990
- OpenAlex
- W2169225609
- Cited by
- 104
- References
- 29
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 10 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 7 · 2012: 6
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Reproduction Fertility and Development (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- 5α-reduction, 5α-reductase, dihydrotestosterone, testosterone, androgen receptor, male development, NADPH cofactor, steroid hormone signaling, hormone-receptor complex, brassinolide, androstanol, androstenol, progesterone, aldosterone, cortisol, plant steroid hormones
- MeSH terms
- Androgens, Animals, Cholestanols, Humans, Isoenzymes, NADP, Plants, Receptors, Androgen, Dihydrotestosterone, Steroids, Heterocyclic, Substrate Specificity, Testosterone, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Brassinosteroids
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