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

基本信息

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

项目摘要

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

研究了成年小鼠肾脏和肝脏中 Cyp2b9 和 Cyp2b10 基因的表达。雌性小鼠肾脏中 CYP2B mRNA 的组成型表达水平高于雄性小鼠，因为肝脏中 CYP2B9 的表达量高于 CYP2B10。在用地塞米松 (Dex) 治疗后，男性肾脏中 CYP2B10 的表达量远高于男性。与 Dex 相比，苯巴比妥 (PB)、孕烯醇酮-16α-甲腈 (PCN) 和 1,1,1-三氯-,2-双(对氯苯基)eihane (DDT) 不诱导的表达。男女肾脏中的 Cyp2b 基因在肝脏中，PB、PCN 和 DDT 均可诱导男女的 CYP2B9 和 CYP2B10。 RU-486（一种糖皮质激素受体拮抗剂）在雄性小鼠的肾脏和肝脏中均降低了 CYP2B10，同时抑制了 CYP2B mRNA 的 Dex 诱导表达。 -486 本身诱导 CYP2B mRNA 的表达，性腺切除术增加了未经治疗的男性肝脏中 CYP2B mRNA 的表达，但抑制了 Dex 诱导的表达。这些观察结果表明，(a) Cyp2b 基因的表达存在多种调节途径，其中 Dex 使用的调节途径是通过糖皮质激素受体介导的，这与 PB 使用的不同。性激素对小鼠 Cyp2b 基因的性别依赖性表达起到调节作用。此外，青春期前小鼠肝脏中 CYP2B mRNA 的组成型表达量为与性别无关，以 CYP2B9 为主要亚型，在成熟阶段，CYP2B10 在两性中均表达，而 CYP2B9 在雄性中显着减少，导致成年小鼠中的性别二态性表达消除。 CYP2B 亚家族通过显着增加男性 CYP2B9 和 CYP2B10 的表达至与女性相似的水平。