Influence of vitamin A status on the regulation of uridine (5′-)diphosphate-glucuronosyltransferase (UGT) 1A1 and UGT1A6 expression by L-triiodothyronine

Abstract

The uridine (5'-)diphosphate-glucuronosyltransferases (UGT) are involved in the phase II of various xenobiotics and endogenous compounds. They are responsible for glucuronidation of many substrates, especially including bilirubin (UGT1A1) and phenolic compounds (UGT1A6). We previously showed that the expression of both isoforms is regulated at the transcriptional level by thyroid hormone in rat liver. In this present study, effects of vitamin A dietary intake (0, 1.72, 69 microg retinol acetate/g food) on the regulation of UGT1A1 and UGT1A6 activity and expression by 3,5,3' triiodo-l-thyronine (l-T3) were examined in the same organ. Activities were determined toward bilirubin and 4-nitrophenol. UGT mRNA were analysed by reverse transcription and amplification methods (reverse transcription-polymerase chain reaction) and quantified by capillary electrophoresis. In rats fed a vitamin A-balanced diet, a single injection of l-T3 (500 microg/kg body weight) increased UGT1A6 mRNA expression whereas this hormone decreased UGT1A1 mRNA expression. In addition we observed that the specific effect of l-T3 on UGT1A1 and UGT1A6 was reduced in animals receiving a vitamin A-enriched diet and disappeared in those fed a vitamin A-free diet. The modulations observed in mRNA expression are concomitant with those found for UGT activities. Our results demonstrate for the first time the existence of a strong interaction between vitamin A and thyroid hormone on the regulation of genes encoding cellular detoxification enzymes, in this case the UGT.