9-cis-Retinoic acid regulation of four UGT isoforms in hepatocytes from rats with various thyroid states.

PURPOSE

To investigate the influence of thyroid hormone status on the regulation of UGTs expression by 9-cis-retinoic acid in cultured rat primary hepatocytes.

METHODS

Hepatocytes from rats with various thyroid states were isolated and treated with 9-cis retinoic acid (1 x 10(-6) M). mRNA was amplified by reverse transcription and polymerase chain reaction (RT-PCR) and quantified by UV light densitometry. Variations in the expression levels of four different UGT isoforms (UGT1A1, 1A2, 1A5, and 1A6) that are involved in the glucuronication of bilirubin and phenols were determined by comparison with those of an internal standard, beta-actin, which is known to be insensitive to nutritional and hormonal conditions.

RESULTS

Primary hepatocyte cultures from rats with various thyroid states present similar metabolite characteristics to those from hypo- or hyperthyroid animals. The treatment of hepatocytes from hypothyroid rats with 9-cis-retinoic acid (1 x 10(-6) M) did not significantly modify bilirubin and phenol-UGT isoform expression. In contrast, in hepatocytes from normal and specially hyperthyroid rats treated with 9-cis-retinoic acid, UGT mRNA levels were modified. This suggests that the effect of retinoic acid on UGT mRNA expression requires the presence of thyroid hormone. This was confirmed by the treatment of cultured hepatocytes from hypothyroid rats with both retinoic acid and L-T3.

CONCLUSIONS

This study demonstrates that in cultured hepatocytes, the thyroid status can differentially modulate the expression of four UGT isoforms, and the regulation of their expression can be affected by 9-cis-retinoic acid.