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

Access this Article

Author(s)

Abstract

ONO-9302 [epristeride; (−)-17β-(<I>tert</I>-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 IC<SUB>50</SUB> 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.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 74(3), 243-252, 1997-07-01

    The Japanese Pharmacological Society

References:  54

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008679192
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4260356
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
Page Top