Different expression mechanism of CYP2B subfamilies by phenobarbital and glucocorticoid hormone

苯巴比妥和糖皮质激素对CYP2B亚家族的不同表达机制

• 批准号: 13672341
• 负责人: NEMOTO Nobuo
• 金额: $ 0.7万
• 依托单位: TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672341/
• 关键词: CYP2B; Sex hormone; Growth hormone; Phenobarbita; シトクロムP450; 性ホルモン

The expression of Cyp2b9 and Cyp2b10 genes was investigated in kidney and liver of adult mice. The constitutive expression level of CYP2B mRNA in kidney was higher in female than in male mice, as it was in the liver where more CYP2B9 than CYP2B10 was expressed in the females, and more CYP2B10 was expressed in the males. After treatment with dexamethasone (Dex), induction of CYP2B10 in the kidneys was far greater in male than in female mice. In contrast to Dex, phenobarbital (PB), pregnenolone-16α-carbonitrile (PCN), and 1,1,1-trichloro- ,2-bis(p-chlorophenyl)eihane (DDT) did not induce the expression of the Cyp2b gene in the kidneys of either sex. In the liver, PB, PCN, and DDT induced both CYP2B9 and CYP2B10 in both sexes to the same extent, whereas Dex induced only CYP2B10 and simultaneously suppressed CYP2B9. Dex-inducible expression of CYP2B mRNA was decreased by RU-486, an antagonist of glucocor-ticoid receptor, in both the kidneys and liver from male mice. However, RU-486 itself … More induced the expression of CYP2B mRNA. Gonadectomy increased the expression of CYP2B mRNA in untreated male liver, but suppressed Dex-induced expression in the kidneys of both sexes. These observations suggest that (a) there are multiple regulatory pathways in the expression of Cyp2b genes, one of which used by Dex is mediated via the glucocorticoid receptor, which is different from that used by PB, and (b) sex hormones play a role in the regulation of the sex-dependent expression of Cyp2b genes in the mouse.Furthermore, the constitutive expression of CYP2B mRNA in the livers of mice in the prepubertal stage was sex-independent, with CYP2B9 as the principal isoform. During the maturation stage, CYP2B10 was expressed in both sexes, whereas CYP2B9 was diminished markedly in the males, resulting in a sexually dimorphic expression in adult mice. Hypophysectomy eliminated the sexual dimorphism in the mouse CYP2B subfamily by markedly increasing the expression of both CYP2B9 and CYP2B10 in males to levels similar to those in females. Less

研究了Cyp2b9和Cyp2b10基因在成年小鼠肾脏和肝脏中的表达。雌性小鼠肾脏中CYP2B mRNA的组成型表达水平高于雄性小鼠，因为在肝脏中，雌性小鼠表达的CYP2B9多于CYP2B10，雄性小鼠表达的CYP2B10多于肝脏。地塞米松（Dex）处理后，雄性小鼠肾脏中CYP2B10的诱导作用远大于雌性小鼠。与Dex相反，苯巴比妥（PB）、双烯醇酮-16 α-腈（PCN）和1，1，1-三氯-，2-双（对氯苯基）乙烷（DDT）在两种性别的肾脏中均不诱导Cyp2b基因的表达。在肝脏中，PB、PCN和DDT在两种性别动物中均以相同程度诱导CYP2B9和CYP2B10，而Dex仅诱导CYP2B10，同时抑制CYP2B9。类糖皮质激素受体拮抗剂RU-486可降低Dex诱导的雄性小鼠肾脏和肝脏CYP2B mRNA的表达。然而，RU-486本身 ...更多信息 诱导CYP2B mRNA的表达。性腺切除术增加CYP2B mRNA的表达在未经处理的男性肝脏，但抑制右旋糖酐诱导的表达在两种性别的肾脏。这些观察结果表明：（a）Cyp2 B基因的表达存在多种调节途径，Dex使用的其中一种途径是通过糖皮质激素受体介导的，这与PB使用的途径不同;（B）性激素在小鼠Cyp2 B基因的性别依赖性表达中起调节作用。青春期前小鼠肝脏中CYP2BmRNA的组成型表达与性别无关，CYP2B9为主要亚型。在成熟阶段，CYP2B10在两种性别中表达，而CYP2B9在雄性中显著减少，导致成年小鼠中的性二态表达。垂体切除通过显著增加雄性中CYP2B9和CYP2B10的表达至与雌性相似的水平来消除小鼠CYP2B亚家族中的两性异形。少

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