| Project/Area Number |
01570900
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | Yokohama City University |
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Principal Investigator |
KINOSHITA Yuzo Yokohama City University School of Medicine. Department of Urology, Assocciate Professor, 医学部, 助教授 (00186298)
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| Co-Investigator(Kenkyū-buntansha) |
HOSAKA Masahiko Yokohama City University School of Medicine. Department of Urology, Professor, 医学部, 教授 (30106330)
野口 和美 横浜市立大学, 医学部付属浦舟病院, 助教授 (10164675)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1989: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | testosterone 5 alpha -reductase / epididymis / estrogens / antiandrogens / down-regulation / 5αーreductase / epididymis / inhibitor / finasteride / LHーRHanalogue / flutamide / ONOー3805 / 5α-還元酵素 / LH-RHアナログ / 阻害剤 |
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| Research Abstract |
The inhibitory effects of various antiandrogens on testosterone 5 alpha -reductase in the human epididymis were studied. In the current study, it was ellucidated that the inhibitory effcts could be obviously devided into two categories : (1) direct inhibitory effect and (2) indirect in hibitory effect. Finasteride and ONO-3805 were potent direct 5 alpha -reductase inhibitor, the former was competitive and the latter noncompetitive. The Ki value in the human epididimal microsomes were 1.3 x 10^<-9>M and 2.5 x 10^<-8>M,respectively. Allylestrenol shows a direct inhibition only in the concentration more than 10^<-4>M and 3-ketoallylestrenol inhibited 5 alpha -reductase in 10^<-8> - 10^<-7>M.Ethynylestradiol, estradiol-17 beta, estriol, estrone were very weak inhibitor and the mode was primarily noncompetitive. The potency of the inhibitory effect by clormadinone acetate and 3 beta -hydroxychlormadinone acetate were also very weak but their inhibition mode was clearly competitive. In spite of the weak potency for the direct inhibition, ethnylestradiol and chlormadinone acetete inhibit human epididymal 5 alpha -reductase very potently. The suppressed 5 alpha -reductase had a significantly decreased Vmax value whereas the Km value was unchanged. The mechanism of inhibition is an indirect type, most probably the downregulation of the 5 alpha -reductase expression through the suppressed hypophyseal-testicular axis.
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