ArticleThe Prostate2014
5α-reductase type 3 enzyme in benign and malignant prostate.
Article in The Prostate, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 42 citations in OpenAlex.
- A reliable transcriptomic risk-score applicable to formalin-fixed paraffin-embedded biopsies improves outcome prediction in localized prostate cancer.Molecular medicine (Cambridge, Mass.) · 2024Article
- Ent-kaurane-type diterpenoids from Isodonis Herba activate human hair follicle dermal papilla cells proliferation via the Akt/GSK-3β/β-catenin transduction pathway.Journal of natural medicines · 2021Article
- Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue.International journal of molecular sciences · 2021Article
- Geranylated Coumarins From Thai Medicinal PlantFrontiers in chemistry · 2020Article
- Potential impact of combined inhibition of 3α-oxidoreductases and 5α-reductases on prostate cancer.Asian journal of urology · 2019Review
- Characterization of Precursor-Dependent Steroidogenesis in Human Prostate Cancer Models.Cancers · 2018Article
- Inhibition of dihydrotestosterone synthesis in prostate cancer by combined frontdoor and backdoor pathway blockade.Oncotarget · 2018Article
- Article
- UDP-glucuronosyltransferases and biochemical recurrence in prostate cancer progression.BMC cancer · 2017Article
- Androgen-glucocorticoid interactions in the era of novel prostate cancer therapy.Nature reviews. Urology · 2016Review
- SRD5A2 gene expression inhibits cell migration and invasion in prostate cancer cell line via F-actin reorganization.Molecular and cellular biochemistry · 2015Article
- Genetic defects in dolichol metabolism.Journal of inherited metabolic disease · 2015Review
- Influence of Panax ginseng on Alpha-Adrenergic Receptor of Benign Prostatic Hyperplasia.International neurourology journal · 2014Article
- Intratumoral steroidogenesis in castration-resistant prostate cancer: a target for therapy.Prostate international · 2014Review
- Effects of different ethanol-administration regimes on mRNA and protein levels of steroid 5α-reductase isozymes in prefrontal cortex of adolescent male rats.Psychopharmacology · 2014Article
- Androgen biosynthesis in castration-resistant prostate cancer.Endocrine-related cancer · 2014Review
- Methylated CpG dinucleotides in the 5-α reductase 2 gene may explain finasteride resistance in benign prostatic enlargement patients.Asian journal of andrologyArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCurrently available 5α-reductase inhibitors are not completely effective for treatment of benign prostate enlargement, prevention of prostate cancer (CaP), or treatment of advanced castration-recurrent (CR) CaP. We tested the hypothesis that a novel 5α-reductase, 5α-reductase-3, contributes to residual androgen metabolism, especially in CR-CaP.
methodsA new protein with potential 5α-reducing activity was expressed in CHO-K1 cellsandTOP10 E. coli for characterization. Protein lysates and total mRNA were isolated from preclinical and clinical tissues. Androgen metabolism was assessed using androgen precursors and thin layer chromatography or liquid chromatography tandem mass spectrometry.
resultsThe relative mRNA expression for the three 5α-reductase enzymes in clinical samples of CR-CaP was 5α-reductase-3 ≫ 5α-reductase-1> 5α-reductase-2. Recombinant 5α-reductase-3 protein incubations converted testosterone, 4-androstene-3,17-dione (androstenedione) and 4-pregnene-3,20-dione (progesterone) to dihydrotestosterone, 5α-androstan-3,17-dione, and 5α-pregnan-3,20-dione, respectively. 5α-Reduced androgen metabolites were measurable in lysates from androgen-stimulated (AS) CWR22 and CR-CWR22 tumors and clinical specimens of AS-CaP and CR-CaP pre-incubated with dutasteride (a bi-specific inhibitor of 5α-reductase-1 and 2).
conclusionHuman prostate tissues contain a third 5α-reductase that was inhibited poorly by dutasteride at high androgen substrate concentration in vitro, and it may promote DHT formation in vivo, through alternative androgen metabolism pathways when testosterone levels are low.
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Registered trials
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