Selectivity of finasteride as an in vivo inhibitor of 5alpha-reductase isozyme enzymatic activity in the human prostate.
The type II 5alpha-reductase inhibitor finasteride is used in the treatment of benign prostatic hyperplasia (BPH), reducing local production of the growth promoting androgen dihydrotestosterone (DHT). The effect of prolonged treatment with this time-dependent irreversible inhibitor on the recently described prostatic type I 5alpha-reductase, however, is not clear. Therefore, we assessed the effects of 5 mg. finasteride per day for 6 months on prostatic 5alpha-reductase isozymes, and prostatic tissue composition and androgen content of patients suffering from BPH. In prostatic tissue from these patients, the type II enzymatic activity is inhibited 100-fold compared with tissues obtained from placebo treated patients. The type II immunoreactivity is up regulated 2-fold. The type I isozyme is inhibited 3-fold and potentially still contributes to DHT production. In conclusion, finasteride is a selective type II inhibitor in vivo. Further research is warranted to assess the possibly distinct roles of the 5alpha-reductase isozymes in the normal prostate, in BPH, and during finasteride treatment.
Department of Internal Medicine, University Hospital St. Radboud, Nijmegen, The Netherlands.
P N
PN
Span
M C
MC
Völler
A G
AG
Smals
F G
FG
Sweep
J A
JA
Schalken
M R
MR
Feneley
R S
RS
Kirby
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000032:analysis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000737:chemistry / Q000201:enzymology*; D011470:Prostatic Hyperplasia / Q000201:enzymology*
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase