Open AccessHormonal Effects of Z-350, Possessing Steroid 5 a-Reductase Inhibitory and a ι-Adrenoceptor Antagonistic Actions, in the Rat
Author(s) -
Youichi Fukuda,
Yoshihisa Fukuta,
Raita Higashino,
Kenji Yoshida,
Masayuki Ogishima,
Makoto Takei,
Tadashi Kurimoto
Publication year - 2001
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.86.323
Subject(s) - endocrinology , medicine , dihydrotestosterone , epididymis , testosterone (patch) , hormone , steroid , prostate , seminal vesicle , chemistry , androgen , sperm , andrology , cancer
We examined the hormonal effects of Z-350, (S)-4-[3-(4-[1-(4-methylphenyl)-3-[4-(2-methoxyphenyl)piperazine-1-yl]propoxy]benzoyl)indole-1-yl]butyric acid hydrochloride, which has both alpha1-adrenoceptor blocking activity and steroid 5alpha-reductase inhibitory activity, in male and female rats. Z-350 administered orally for 14 days at a dose of 30 mg/kg to normal male rats significantly reduced the weight of the prostate and seminal vesicles without affecting the weight of the testis, epididymis, adrenals, kidney or liver. Prostatic levels of dihydrotestosterone decreased dose-dependently, with a slight increase in the level of testosterone at a Z-350 dose of 100 mg/kg. We observed no effects on the weight of the prostate in castrated rats or on the weight of the uterus in normal or 17beta-estradiol-treated female rats. These results suggest that Z-350 inhibits prostatic growth via inhibition of steroid 5-reductase without other hormonal effects.