Jpn. J. Pharmacol. 74, 243-252 (1997)

Effects of Steroid 5alpha-Reductase Inhibitor ONO-9302 and Anti-Androgen Allylestrenol on the Prostatic Growth, and Plasma and Prostatic Hormone Levels in Rats

Naohiro Yasuda, Katsuhiro Fujino, Takamitsu Shiraji, Fumio Nambu and Kigen Kondo

Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., 3-1-1, Sakurai Shimamoto-cho, Mishima-gun, Osaka 618, Japan

Abstract: ONO-9302 [epristeride; (-)-17beta-(tert-butylcarbamoyl)androsta-3,5-diene-3-carboxylic acid] is a novel inhibitor of steroid 5alpha-reductase. We studied in vitro and in vivo effects of ONO-9302 on the rat prostatic tissue in comparison with those of the anti-androgen allylestrenol. ONO-9302 inhibited the rat prostatic enzyme with an IC50 value of 11 nM, whereas allylestrenol was about 80,000-fold less potent. The growth of ventral prostate, which was induced by the subcutaneous injection of testosterone propionate in the castrated rats, was significantly reduced by ONO-9302 at oral doses of 1 - 100 mg/kg/day. Allylestrenol showed a significant effect only at a dose of 100 mg/kg/day. In mature male rats, ONO-9302 significantly reduced the ventral prostate weight at doses of 10 - 100 mg/kg/day and decreased prostatic 5alpha-dihydrotestosterone (DHT) content associated with a rise in testosterone (T) content at doses of 0.1 - 100 mg/kg/day. Plasma hormone levels (i.e., T, DHT, luteinizing hormone (LH) and follicle stimulating hormone (FSH)) were not altered significantly. Allylestrenol significantly reduced the ventral prostate weight at doses of 10 - 100 mg/kg/day. However, unlike ONO-9302, allylestrenol reduced both the prostatic DHT and T contents and also lowered plasma T, DHT, LH and FSH levels at a dose of 30 mg/kg/day. These results suggest that ONO-9302 reduces the prostatic growth by inhibiting the conversion of T to DHT in the prostate without lowering blood T level unlike anti-androgen drugs.

Keywords: Steroid 5alpha-reductase, Dihydrotestosterone, Testosterone, Prostate, ONO-9302

Copyrightę The Japanese Pharmacological Society 1997

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