Novel nonsteroidal inhibitor of cytochrome P45017α (17α-hydroxylase/C17–20 lyase), YM116, decreased prostatic weights by reducing serum concentrations of testosterone and adrenal androgens in rats
✍ Scribed by Ideyama, Yukitaka; Kudoh, Masafumi; Tanimoto, Kyoko; Susaki, Yoko; Nanya, Taiki; Nakahara, Takahito; Ishikawa, Hiroko; Yoden, Toru; Okada, Minoru; Fujikura, Takashi; Akaza, Hideyuki; Shikama, Hisataka
- Book ID
- 101224412
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 257 KB
- Volume
- 37
- Category
- Article
- ISSN
- 0270-4137
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✦ Synopsis
Background:
The purpose of this study was to determine the effects of a nonsteroidal c17-20 lyase inhibitor, 2-(1h-imidazol-4-ylmethyl)-9h-carbazole (ym116), on serum concentrations of androgens and ventral prostatic weight in rats.
Methods:
Serum concentrations of testosterone and of dehydroepiandrosterone sulfate and prostatic weights were measured in rats treated with ym116.
Results:
Ym116 inhibited testicular c17-20 lyase competitively (ki, 0.38 nm), and decreased the serum testosterone concentration in gonadotropin-releasing hormone-treated rats (ed50, 0.7 mg/kg), indicating that ym116 was about 21-24 times more potent than other c17-20 lyase inhibitors such as ketoconazole and liarozole, and was twice as potent as cb7630. ym116 also reduced dehydroepiandrosterone sulfate levels in acth-treated castrated rats (ed50, 11 mg/kg). ym116 (40 mg/kg, p.o., for 2 weeks) was almost comparable to bilateral orchiectomy with respect to the time course and magnitude of the reduction in prostatic weight. each of these two treatments decreased the prostatic weight 3 days following the treatment. contrarily, leuprolide transiently increased the prostatic weight and then decreased it. ym116 (100 mg/kg) had no effect on the serum cortisol level in guinea pigs, and slightly decreased the serum aldosterone level in rats.
Conclusions:
Ym116 is a selective c17-20 lyase inhibitor which decreases rat prostatic weight by reducing androgen production in the testes and adrenal glands.