Effects of 5 alpha-reductase inhibitors on intraprostatic androgens in the rat.
FCE 27837 is a novel inhibitor of 5 alpha-reductase, the enzyme responsible for the conversion of testosterone (T) to 5 alpha-dihydrotestosterone (DHT). The compound caused inhibition of human and rat prostatic enzymes, with IC50 values of 51 and 60 nM, respectively. The in vivo effect of FCE 27837 on 5 alpha-reductase was evaluated in adult male rats, treated orally at 10 mg/kg/day for 10 days. The compound caused 33 and 42% reductions in ventral prostate and seminal vesicle weights, respectively. The prostatic content of DHT, measured 6 h after the 10th dose of FCE 27837, was reduced by 75%, whereas T content increased by 442%. Similar effects were observed with 10 mg/kg/day of finasteride, whereas epristeride, tested at the same oral dose, was found to be the least effective compound, decreasing prostate weight by 22% and DHT content by 46%. Castration caused > 90% reductions in prostatic weight and prostatic DHT.
di Salle
E
E
Experimental Endocrinology Department, R&D Oncology, Nerviano (MI), Italy.
Giudici
D
D
Biagini
L
L
Cominato
C
C
Briatico
G
G
Panzeri
A
A
D000730:Androstadienes / Q000494:pharmacology; D000736:Androstenes / Q000494:pharmacology*; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology*; D042944:Cholestenone 5 alpha-Reductase; D013196:Dihydrotestosterone / Q000378:metabolism*; D018120:Finasteride / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011467:Prostate / Q000378:metabolism*; D051381:Rats; D013739:Testosterone / Q000378:metabolism*
D000730:Androstadienes; D000736:Androstenes; D001378:Azasteroids; D013196:Dihydrotestosterone; C088572:FCE 27837; C072547:epristeride; D013739:Testosterone; D018120:Finasteride; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase