New frontiers in androgen biosynthesis and metabolism
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PURPOSE OF REVIEW: To summarize recent advances in androgen biosynthesis and metabolism in peripheral tissues (e.g., liver and prostate) and how these can be exploited therapeutically. RECENT FINDINGS: Human liver catalyzes the reduction of circulating testosterone to yield four stereoisomeric tetrahydrosteroids. Recent advances have assigned the enzymes responsible for these reactions and elucidated their structural biology. Data also suggest that for 5alpha-dihydrotestosterone (5alpha-DHT), conjugation reactions (phase II) may precede ketosteroid reduction (phase I) reactions. Human prostate is the site of benign prostatic hyperplasia and prostate cancer, which occur in the aging male. Although the importance of local androgen biosynthesis in these diseases is accepted, recent advances have identified enzymes that regulate ligand access to the androgen-receptor; a 'backdoor pathway' to 5alpha-DHT that does not require testosterone acting as an intermediate; and the finding that castrate-resistant prostate cancer (CRPC) has undergone an adaptive response to androgen deprivation, which involves intratumoral testosterone and 5alpha-DHT biosynthesis that can be targeted using inhibitors of (CYP17-hydroxylase/17,20-lyase), aldo-keto reductase 1C3, and 5alpha-reductase type 1 and type 2. SUMMARY: Enzyme isoforms responsible for the biosynthesis and metabolism of androgens in liver and prostate have been identified and those responsible for the biosynthesis of androgens in CRPC can be therapeutically targeted.
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A-ring reduction consists of two sequential reductions, namely reduction of Δ4-double bond followed by reduction of 3-keto group to hydroxy group.
“A-ring reduction consists of two sequential reductions, namely the reduction of the Δ4-double bond followed by the reduction of the 3-keto group to a hydroxy group [92] (Fig. 4(a)).”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [92]
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- Authors
- Penning, T. M.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Penning, Trevor M
- ORCID
- Penning, Trevor M
- Venue
- Current Opinion in Endocrinology, Diabetes & Obesity
- Published
- 2010-06
- Volume
- 17
- Issue
- 3
- Pages
- 233-239
- ISSN
- 1752-296X (ISSN-L)
- PMC
- PMC3206266
- OpenAlex
- W2059535338
- Cited by
- 51
- References
- 64
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 1 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 5 · 2012: 7
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Endocrinology Diabetes and Obesity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (1R01-CA90744, R01CA090744)
- National Institute of Diabetes and Digestive and Kidney Diseases (1R01-DK47015, R01DK047015)
- National Institute of Environmental Health Sciences (P30ES013508)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- androgen production, androgen metabolism, liver, prostate, testosterone suppression, dihydrotestosterone, conjugation, benign prostatic hyperplasia, prostate cancer, castration-resistant prostate cancer, androgen receptor, CYP17, aldo-keto reductase 1C3, 5α-reductase, isozymes, therapeutic target
- MeSH terms
- Aldo-Keto Reductases, Alcohol Oxidoreductases, Aldehyde Reductase, Androgens, Humans, Liver, Male, Prostate, Prostatic Neoplasms, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Biomedical Research
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