Androgen biosynthetic pathways in the human prostate

Luu-The, Van; Bélanger, Alain; Labrie, Fernand

doi:10.1016/j.beem.2008.01.008

Cited by 173Prostate Cancer Treatment and ResearchHormonal and reproductive studiesSperm and Testicular Function

Androgen biosynthetic pathways in the human prostate

Luu-The, Van, Bélanger, Alain, Labrie, Fernand·2008·Best Practice & Research Clinical Endocrinology & Metabolism

DOI 10.1016/j.beem.2008.01.008

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Abstract

It is well recognized that there are two androgens, namely testosterone (T) and dihydrotestosterone (DHT); T plays an important role in the testis and muscle, and DHT is crucial for the development, function and pathology of the prostate. It is generally thought that DHT is produced from the 5alpha-reduction of circulating T before being inactivated by 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) that converts DHT into 5alpha-androstane-3alpha,17beta-diol (3alpha-diol). However, the presence of various steroidogenic enzymes in the prostate as well as the availability at high levels of various steroid precursors such as dehydroepiandrosterone sulphate (DHEAS), dehydroepiandrosterone (DHEA) and 4-androstenedione (4-dione) strongly suggest the existence of additional pathways involved in the biosynthesis and metabolism of DHT. Because steroidogenesis could be different in different species, data from the literature obtained from various human, dog, rat and mouse prostate tissues, as well as primary cells and prostatic cancer cell lines, provide a somewhat confusing picture. In the present chapter, we review the data in order to provide a clearer picture of the pathways involved in DHT biosynthesis and metabolism in the human prostate.

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CRPC is dependent on the intracrine conversion of circulating androgen precursors of adrenal origin to active androgens.
“numerous studies have shown that CRPC is dependent on the intracrine conversion of circulating androgen precursors of adrenal origin to active androgens reviewed in (Capper et al., 2016, Luu-The et al., 2008, Pretorius et al., 2017, Sharifi and Auchus, 2012).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Luu-The et al., 2008

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Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer
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Intracrine Regulation of Estrogen and Other Sex Steroid Levels in Endometrium and Non-gynecological Tissues; Pathology, Physiology, and Drug Discovery
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Review article: the role of HSD17B13 on global epidemiology, natural history, pathogenesis and treatment of NAFLD
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11β-Hydroxyandrostenedione Returns to the Steroid Arena: Biosynthesis, Metabolism and Function
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The Stimulation of HSD17B7 Expression by Estradiol Provides a Powerful Feed-Forward Mechanism for Estradiol Biosynthesis in Breast Cancer Cells
Shehu, A., Albarracin, C. T., Devi, Y. S., Luther, K. M., Halperín, J., Le, J., Mao, J., Duan, R. W., Frasor, J. M., & Gibori, G. (2011) · Molecular Endocrinology · doi:10.1210/me.2010-0261 · Cited by 54 · see citing works
Androgens and esophageal cancer: What do we know?
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Activin A Stimulates AKR1C3 Expression and Growth in Human Prostate Cancer
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Identification of a 17β‐Hydroxysteroid Dehydrogenase Type 10 Steroidal Inhibitor: A Tool to Investigate the Role of Type 10 in Alzheimer’s Disease and Prostate Cancer
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Inverse Regulation of DHT Synthesis Enzymes 5α-Reductase Types 1 and 2 by the Androgen Receptor in Prostate Cancer
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A New Nonestrogenic Steroidal Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type I Blocks the Estrogen-Dependent Breast Cancer Tumor Growth Induced by Estrone
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Direct Metabolic Interrogation of Dihydrotestosterone Biosynthesis from Adrenal Precursors in Primary Prostatectomy Tissues
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DNA methylation screening of primary prostate tumors identifies SRD5A2 and CYP11A1 as candidate markers for assessing risk of biochemical recurrence
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GnRH agonists and the rapidly increasing use of combined androgen blockade in prostate cancer
Labrie, F. (2014) · Endocrine Related Cancer · doi:10.1530/erc-13-0165 · Cited by 42 · see citing works
Loss of an Androgen-Inactivating and Isoform-Specific HSD17B4 Splice Form Enables Emergence of Castration-Resistant Prostate Cancer
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Human microsomal carbonyl reducing enzymes in the metabolism of xenobiotics: well-known and promising members of the SDR superfamily
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Hormonal Therapy of Prostate Cancer
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Development of 3-substituted-androsterone derivatives as potent inhibitors of 17β-hydroxysteroid dehydrogenase type 3
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New agents and strategies for the hormonal treatment of castration-resistant prostate cancer
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A high-throughput UPC2-MS/MS method for the separation and quantification of C19 and C21 steroids and their C11-oxy steroid metabolites in the classical, alternative, backdoor and 11OHA4 steroid pathways
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Expression Patterns of 17β-Hydroxysteroid Dehydrogenase 14 in Human Tissues
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Authors: Luu-The, V., Bélanger, A., & Labrie, F.
Affiliations: Université Laval (CA)
Corresponding author: Luu-The, Van
Venue: Best Practice & Research Clinical Endocrinology & Metabolism
Publisher: Elsevier BV
Published: 2008-04
Volume: 22
Issue: 2
Pages: 207-221
ISSN: 1521-690X (ISSN-L)
DOI: 10.1016/j.beem.2008.01.008
OpenAlex: W2007245161
Cited by: 169
References: 110
Citations by year: 2026: 3 · 2025: 1 · 2024: 1 · 2023: 5 · 2022: 9 · 2021: 5 · 2020: 1 · 2019: 11 · 2018: 9 · 2017: 8 · 2016: 11 · 2015: 9 · 2014: 9 · 2013: 16 · 2012: 18
FWCI: 2.85
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Best Practice & Research Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
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, dihydrotestosterone, testosterone, human prostate, 5α-reduction, 3α-hydroxysteroid dehydrogenase, 3alpha-diol, dehydroepiandrosterone sulfate, dehydroepiandrosterone, 4-androstenedione, steroidogenic enzymes, prostate cancer
MeSH terms: Androgens, Animals, Humans, Hydroxysteroid Dehydrogenases, Male, Models, Biological, Oxidoreductases, Prostate, Dihydrotestosterone, Testosterone, Biosynthetic Pathways

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Androgen biosynthetic pathways in the human prostate

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