Cited by 62Prostate Cancer Treatment and ResearchPharmacogenetics and Drug MetabolismDrug Transport and Resistance Mechanisms

Multiple roles for UDP-glucuronosyltransferase (UGT)2B15 and UGT2B17 enzymes in androgen metabolism and prostate cancer evolution

Gauthier-Landry, Louis, Bélanger, Alain, Barbier, Olivier·2015·The Journal of Steroid Biochemistry and Molecular Biology

Abstract

In the prostate, approximately 50% of androgens are from adrenal steroids, mainly dehydroepiandrosterone (DHEA), its sulfate and androstenedione. These compounds are converted first into testosterone, and then into the active hormone dihydrotestosterone (DHT). After having activated the androgen receptor (AR), DHT is reduced into androstane-3α-DIOL (3α-DIOL) and androsterone (ADT), which are subsequently converted into 2 inactive and easily excretable metabolites: 3α-DIOL-17glucuronide (3α-DIOL-17G) and ADT-3glucuronide (ADT-3G). The formation of these last derivatives through the glucuronidation reaction involves 2 UDP-glucuronosyltransferase (UGT) enzymes, namely UGT2B15 and UGT2B17. The present review article aims at providing a comprehensive view of the physiological and pharmacological importance of these 2 enzymes for the control of androgen homeostasis. We will resume: (i) how UGT2B15 and UGT2B17 contribute to androgen elimination; (ii) how their glucuronidation capacity influences the androgen signaling pathway in prostate cells; (iii) how they contribute to the anti-proliferative properties of AR antagonists in prostate cancer cells; and (iv) how AR and its spliced variants regulate the UGT2B15 and/or UGT2B17 genes expression. Finally, whether the unexploited AR-UGT axis could serve as a prognostic maker or a pharmacological target for novel therapeutics in the treatment of prostate cancer is also discussed. This article is part of a special issue entitled 'Essential role of DHEA'.

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Crossref · 10.1016/j.jsbmb.2014.05.009

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  • Down-regulation of UGTs in prostate cancer promotes intratumoral androgen accumulation.

    “Genetic variations of UGTs significantly contribute to prostate cancer risk and progression and there is evidence for a down-regulation of UGTs in prostate cancer promoting intratumoral androgen accumulation (Barbier and Belanger, 2008, Gauthier-Landry et al., 2015).”

    From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Gauthier-Landry et al., 2015

  • Genetic variations of UGTs significantly contribute to prostate cancer risk and progression.

    “Genetic variations of UGTs significantly contribute to prostate cancer risk and progression and there is evidence for a down-regulation of UGTs in prostate cancer promoting intratumoral androgen accumulation (Barbier and Belanger, 2008, Gauthier-Landry et al., 2015).”

    From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Gauthier-Landry et al., 2015

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Authors
Gauthier-Landry, L., Bélanger, A., & Barbier, O.
Affiliations
Université Laval (CA)
Corresponding author
Barbier, Olivier
Venue
The Journal of Steroid Biochemistry and Molecular Biology
Publisher
Elsevier BV
Published
2015-01
Volume
145
Pages
187-192
ISSN
0960-0760 (ISSN-L)
OpenAlex
W2159660532
Cited by
62
References
82
Citations by year
2026: 3 · 2025: 1 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 9 · 2017: 9 · 2016: 7 · 2015: 6
FWCI
1.26
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • CIHR
  • Natural Sciences and Engineering Research Council of Canada
  • Canadian Foundation for Innovation
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
UGT2B15, UGT2B17, UDP-glucuronosyltransferase, androgen metabolism, prostate cancer, androgen receptor, glucuronidation, androgen receptor antagonists, androgen receptor splice variants, prognostic factors, therapeutic target, dehydroepiandrosterone, androstenedione, dihydrotestosterone
MeSH terms
Androgens, Gene Expression Regulation, Humans, Male, Prognosis, Prostate, Prostatic Neoplasms, Receptors, Androgen, Glucuronosyltransferase, Minor Histocompatibility Antigens, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Cell Proliferation

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