The effect of hormones on the expression of five isoforms of UDP-glucuronosyltransferase in primary cultures of rat hepatocytes

Purpose. To investigate the direct effects of sex hormones, growth hormone, thyroid hormones and dexamethasone on the regulation of UDP-glucuronosyltr ansferase (UGT). Methods. Rat hepatocytes were cultured on matrigel and treated with various hormones. Northern blot analysis was carried out using cDNA probes to fami ly 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 effe ct on the expression of UGT 1 isoforms, with increased UGT1A6 by 70%, and d ecreased UGT1A1 by 38% and UGT1A5 by 35%. All UGT isoforms except UGT 1A6 s tudied in this assay were up-regulated by dexamethasone, but to different d egrees. The regulation of UGT1A1 and UGT2B1 by dexamethasone was dose and t ime dependent, and the induction of dexamethasone in the expression of UGT1 A1 and UGT2B1 was blocked by cycloheximide but not dichloro-1-D-ribofuranos ylbenzimidazole. Conclusions. This study demonstrates that multiple hormones take part in th e regulation of UGT mRNA expression in the rat and individual genes can be differentially modulated.