Molecular mechanism of development and regulation of sex-specific cytochrome P-450 in rat liver

大鼠肝脏性别特异性细胞色素P-450发育和调控的分子机制

• 批准号: 59440027
• 负责人: KATO Ryuichi
• 金额: $ 12.8万
• 依托单位: School of Medicine, Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-59440027/
• 关键词: 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

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.

研究了大鼠肝细胞色素P-450性别特异性发育和调控的分子机制，发现大鼠肝细胞色素P-450性别特异性发育受调控，雄性P-450和雌性P-450均受调控。雄激素刺激P-450-male的表达，抑制P-450-male的表达，雌激素强烈抑制P-450-male的表达，垂体切除减少P-450-male，但完全抑制P-450-female，表达P-450-male。此外，生长激素表达或抑制P-450-雄性依赖于给药方式。吗啡、利血平和四氧嘧啶处理的雄性大鼠P-450-male降低，相同处理的雌性大鼠P-450-male表达。睾酮16<alpha>-羟化的变化与P-450-雄的变化密切相关，因此睾酮被认为是P-450-雄的内源性底物，此外，苯并（a）芘羟化酶与P-450-雄相关。还研究了两个新的性别特异性P-450的调节，这两个新的性别特异性P-450负责睾酮6<beta>-羟基化，P-450-6<beta>-<I>和P-450-6<beta>-<II>。

项目成果

Yamazoe, Y., Shimada, M., Kamataki, T. and Kato, R.: "Effects of hypophysectomy and growth hormone treatment on sex-specific forms of cytochrome P-450 in relation to drug and steroid metabolisms in rat liver microsomes." Japan. J. Pharmacol.42. 371-382 (1

Yamazoe, Y.、Shimada, M.、Kamataki, T. 和 Kato, R.：“垂体切除术和生长激素治疗对细胞色素 P-450 性别特异性形式的影响，与大鼠肝微粒体中药物和类固醇代谢有关。

Kato, R., Yamazoe, Y., Shimada, M., Murayama, N. and Kamataki, T.: "Effect of growth hormone and ectopic transplantation of pituitary gland on sex-specific forms of cytochrome P-450 and testosterone and drug oxidations in rat liver." J. Biochem.100. 895-9

Kato, R.、Yamazoe, Y.、Shimada, M.、Murayama, N. 和 Kamataki, T.：“生长激素和垂体异位移植对细胞色素 P-450 和睾酮和药物的性别特异性形式的影响

Kamataki, T., Maeda, K., Shimada, M., Kitani, K., Nagai, T. and Kato, R.: "Age-related alteration in the activities of drug-metabolizing enzymes and contents of sex-specific forms of cytochrome P-450 in liver microsomes From male and female rats." J. Phar

Kamataki, T.、Maeda, K.、Shimada, M.、Kitani, K.、Nagai, T. 和 Kato, R.：“药物代谢酶活性和性别特异性形式含量的年龄相关变化

Biochem.Biophys.Res.Commun.130-3. (1985)

Biochem.Biophys.Res.Commun.130-3。

Kato,R.;Yamazoe,Y.;Shimada,M.;Murayama,M.;Kamatani,T.: J.Biochem.,. 100. 895-902 (1986)

加藤，R.；山添，Y.；岛田，M.；村山，M.；镰谷，T.：J.Biochem.，。