| Project/Area Number |
59440027
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | School of Medicine, Keio University |
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Principal Investigator |
KATO Ryuichi Professor, School of Medicine, Keio University, 医学部, 教授 (40112685)
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| Co-Investigator(Kenkyū-buntansha) |
YASUMORI Toshio Assistant prof., School of Medicine, Keio University, 医学部, 助手 (70182350)
NAGATA Kiyoshi Assistant prof., School of Medicine, Keio University, 医学部, 助手 (80189133)
YAMAZOE Yasushi Associate prof., School of Medicine, Keio University, 医学部, 講師 (00112699)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥20,000,000 (Direct Cost: ¥20,000,000)
Fiscal Year 1986: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1985: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1984: ¥12,000,000 (Direct Cost: ¥12,000,000)
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| Keywords | sex-specific cytochrome P-450 / androgen / estrogen / growth hormone / testosterone hydroxylation / アンドロジェン / 薬物代謝酵素 / テストステロン水酸化 / チトクロムP-450 / 雌雄固有 / 脳下垂体 / アミノ酸セクエンス |
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| Research Abstract |
Molecular mechanism of development and regulation of sex-specific cytochrome P-450 in rat liver was studied.
Sex-specific cytochrome P-450, P-450-male and P-450-female are developmentally regulated. Androgen stimulates the expression of P-450-male and suppresses the expression of P-450-male and estrogen strongly suppresses the expression of P-450-male.
Hypophysectomy decreases P-450-male but completely suppresses P-450-female in male rats and expresses P-450-male. Moreover, growth hormone expresses or supresses P-450-male dependent upon the mode of administration. P-450-male is decreased in male rats treated with morphine, reserpine or alloxan and P-450-male is expressed in female rats by the same treatments. The change of testosterone 16 <alpha> -hydroxylation is closely correlated to that of P-450-male, thus testosterone is considered as an endogenous substrate of P-450-male.
In addition, benzo(a)pyrene hydroxylase is correlated with P-450-male. Regulation of two new sex-specific P-450, which are responsible for testosterone 6 <beta> -hydroxylation, P-450-6 <beta> - <I> and P-450-6 <beta> - <II> was also studied.
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