Comparison of testosterone metabolism in benign prostatic hyperplasia and human prostate cancer cell lines in vitro.
Pathways of testosterone metabolism in tissue slices and cell suspensions of human benign hyperplastic prostate (BPH) tissue and human prostate cancer cell lines (DU145, HPC-36M, PC-3/MA2 and LNCaP) were investigated. Thin layer chromatography analysis was used to identify the following tritiated metabolites: testosterone, 5 alpha-dihydrostestosterone (DHT), 5 alpha-androstane-3 alpha/3 beta-17 beta-diol (androstanediols), 4-androstene-3,17-dione (androstenedione) and 5 alpha-androstanedione. The predominant pathway for testosterone metabolism in BPH was via 5 alpha-reductase producing 5 alpha-dihydrotestosterone (71% and 75% total metabolites in slices and suspensions incubated for 24 h, respectively). The cancer cell lines DU145 and HPC-36M resembled BPH by metabolizing testosterone predominantly to DHT (68% and 82% total metabolites, respectively), although the rate of metabolism was much lower in the cell lines (0.099 and 0.05 pmol testosterone/mg protein/h in DU145 and HPC-36M) compared to the BPH cell suspensions (6.4 pmol testosterone/mg protein/h). In contrast, PC-3/MA2 contained high 17 beta-HSD activity forming large amounts of 4-androstene-3,17-dione (84% total metabolites), converting testosterone at a rate faster (12.8 pmol testosterone/mg protein/h) than the BPH cell suspensions. LNCaP rapidly converted testosterone exclusively to a glucuronide conjugate (7.4 pmol testosterone/mg protein/h), although after incubation with [3H]-4-androstene-3,17-dione, 5 alpha-reductase activity was demonstrated. LNCaP was the only cell line whose growth and colony-forming ability was stimulated by testosterone and DHT. BPH and all the cell lines tested had 5 alpha-reductase activity, but only the prostate tissue and the cell lines DU145 and HPC-36M converted testosterone predominantly to DHT.
Smith
C M
CM
University College London, Institute of Urology, U.K.
Ballard
S A
SA
Wyllie
M G
MG
Masters
J R
JR
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D013196:Dihydrotestosterone / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase