激素对尿苷二磷酸葡萄糖醛酸基转移酶表达的影响

目的 :探讨性激素、促生长素、甲状腺素和糖皮质激素对UDP 葡萄糖醛酸基转移酶 (UGT)表达的调节作用。方法 :应用原始鼠肝细胞培养及Northernblot杂交技术 ,观察不同种类激素处理肝细胞前后UGT同工酶mRNA的变化。结果 :加用 10 -5mol L浓度的睾酮处理鼠肝细胞后 ,UGT2B1和UGT2B3mRNA表达水平分别增加 2 9%和 32 % ;以 10mIU L促生长素处理肝细胞后 ,UGT2B1和UGT2B3mRNA表达水平分别减少 17%和 38% ;在鼠肝细胞的培养基中加入甲状腺素T3可使UGT1A6的表达增加 70 % ,但UGT1A1、UGT1A5分别减少 38%、35 % ;地塞米松可增加UGT1A1、UGT1A5、UGT2B1和UGT2B3的表达 ,但其增高的幅度不同。地塞米松对UGT1A1和UGT2B1表达的调节作用具有时间及剂量依赖效应。结论 :性激素、促生长素、甲状腺素和地塞米松可调节鼠肝细胞UGTmRNA的表达 ,且对不同种UGTmRNA的调节有所差异。

The regulation of UDP-glucuronosyltransferase mRNA expression by various hormones

Objective:To investigate the direct effects of sex hormones, growth hormone, thyroid hormones and dexamethasone on the regulation of UDP glucuronosyltransferase (UGT).Methods:Rat hepatocytes were cultured on matrigel and treated with various hormones. Northern blot analysis was carried out using cDNA probes to family 1 and family 2 isoforms of UGT.Results:Treatment with 10 -5 mol/L testosterone increased the mRNA levels of UGT 2B1 by 29% and UGT2B3 by 32%. Incubation of hepatocytes (10mU) with growth hormone suppressed the expression of UGT2B1 and UGT2B3 by 17% and 38% respectively. T3 administration resulted in a time and dose dependent effect on the expression of UGT 1 isoforms, with UGT1A6 increased by 70% , and UGT1A1 decreased by 38% and UGT1A5 by 35%. UGT1A1,UGT1A5,UGT2B1 and UGT2B3 were all up regulated by dexamethasone to varying degrees. The regulation of UGT1A1 and UGT2B1 by dexamethasone was dose and time dependent.Conclusion:This study demonstrates that various hormones take part in the regulation of UGT mRNA expression in the rats and individual genes can be differentially modulated.