激素对大鼠肝细胞原代培养物中尿苷二磷酸葡萄糖醛酸基转移酶五种同工型表达的影响。
The effect of hormones on the expression of five isoforms of UDP-glucuronosyltransferase in primary cultures of rat hepatocytes.
作者信息
Li Y Q, Prentice D A, Howard M L, Mashford M L, Desmond P V
机构信息
Department of Gastroenterology, St. Vincent's Hospital, Fitzroy, Victoria, Australia.
出版信息
Pharm Res. 1999 Feb;16(2):191-7. doi: 10.1023/a:1018812021549.
PURPOSE
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.
RESULTS
Treatment with 10(-5) M testosterone increased the mRNA levels of UGT 2B1 by 29% and UGT2B3 by 32%. Incubation of growth hormone (10 mU) with hepatocytes 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 increased UGT1A6 by 70%, and decreased UGT1A1 by 38% and UGT1A5 by 35%. All UGT isoforms except UGT 1A6 studied in this assay were up-regulated by dexamethasone, but to different degrees. The regulation of UGT1A1 and UGT2B1 by dexamethasone was dose and time dependent, and the induction of dexamethasone in the expression of UGT1A1 and UGT2B1 was blocked by cycloheximide but not dichloro-1-D-ribofuranosylbenzimidazole.
CONCLUSIONS
This study demonstrates that multiple hormones take part in the regulation of UGT mRNA expression in the rat and individual genes can be differentially modulated.
目的
研究性激素、生长激素、甲状腺激素和地塞米松对尿苷二磷酸葡萄糖醛酸基转移酶（UGT）调节的直接作用。
方法
将大鼠肝细胞培养于基质胶上，并用各种激素进行处理。使用针对1家族和2家族同工型的cDNA探针进行Northern印迹分析。
结果
用10⁻⁵ M睾酮处理可使UGT 2B1的mRNA水平增加29%，UGT2B3的mRNA水平增加32%。生长激素（10 mU）与肝细胞孵育分别使UGT2B1和UGT2B3的表达抑制了17%和38%。给予T3对UGT 1同工型的表达产生时间和剂量依赖性影响，UGT1A6增加70%，UGT1A1降低38%，UGT1A5降低35%。在本试验中研究的除UGT 1A6外的所有UGT同工型均被地塞米松上调，但程度不同。地塞米松对UGT1A1和UGT2B1的调节呈剂量和时间依赖性，地塞米松对UGT1A1和UGT2B1表达的诱导被放线菌酮阻断，但未被二氯-1-D-呋喃核糖基苯并咪唑阻断。
结论
本研究表明多种激素参与大鼠UGT mRNA表达的调节，且各个基因可被差异调节。
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