title: 5 alpha-reductase activity in cultured epithelial and stromal cells from normal and hyperplastic human prostates--effect of finasteride (Proscar), a 5 alpha-reductase inhibitor.
abstract: Benign prostatic hyperplasia (BPH) is the most common benign proliferative disorder of unknown etiology found in men. Dysregulation of testosterone conversion to dihydrotestosterone (DHT) by 5 alpha-reductase has been described as a key step in the development of BPH. We investigated the 5 alpha-reductase activity in primary cultures of epithelial and stromal cells from the four different regions (periurethral, transition, central and peripheral zones) of normal and hyperplastic human prostates. No significant difference in DHT production was observed among the four epithelial zones and the hyperplastic epithelial cells, or among the four normal zones and the hyperplastic stromal cells. To investigate whether the two known 5 alpha-reductase isoenzymes were expressed in prostate, we performed specific enzymatic amplification after reverse transcription which showed the presence of 274 and 383 base-pair fragments, respectively, specific for 5 alpha-reductase type 1 and 5 alpha-reductase type 2, demonstrating the expression of mRNA for both isoenzymes in BPH tissue. To pharmacologically characterize the isoenzyme present in the two cell components of hyperplastic prostate, we used finasteride, a well known inhibitor specific to 5 alpha-reductase type 2, which only slightly inhibits 5 alpha-reductase type 1. In BPH, IC50 was estimated at 62 nM and 45 nM, for stromal and epithelial cells respectively, suggesting predominately 5 alpha-reductase type 2 activity. Our results provide further evidence that 5 alpha-reductase type 2 activity is mainly responsible for DHT production by human prostatic cells.
authors: Centre de Recherches de l'Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lapeyronie, Montpellier, France.
authors: C
authors: C
authors: Boudon
authors: J M
authors: JM
authors: Lobaccaro
authors: S
authors: S
authors: Lumbroso
authors: E
authors: E
authors: Lechevallier
authors: N
authors: N
authors: Mottet
authors: B
authors: B
authors: Gibelin
authors: C
authors: C
authors: Sultan
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D042944:Cholestenone 5 alpha-Reductase; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D013196:Dihydrotestosterone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000201:enzymology; D018120:Finasteride / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D013196:Dihydrotestosterone; D018120:Finasteride; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase