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

The Japanese Journal of Pharmacology

Takamitsu Shiraji¹  Naohiro Yasuda¹  Kigen Kondo¹  Katsuhiro Fujino¹  Fumio Nambu¹ 

[1] Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd.

关键词: Steroid 5α-reductase;    Dihydrotestosterone;    Testosterone;    Prostate;    ONO-9302;   

DOI  :  10.1254/jjp.74.243

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(54)Cited-By(7)ONO-9302 [epristeride; (−)-17β-(tert-butylcarbamoyl)androsta-3, 5-diene-3-carboxylic acid] is a novel inhibitor of steroid 5α-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 5α-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.

【 授权许可】

Unknown