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.