Vitamin A modulates the effects of thyroid hormone on UDP-glucuronosyltransferase expression and activity in rat liver.

We studied the influence of thyroid hormones and vitamin A status on the regulation of UDP-glucuronosyltransferase (UGT) expression and the glucuronidation of thyroid hormones by UGTs. For this, we used an original model of rats fed with different vitamin A diets and implanted subcutaneously by osmotic minipumps delivering vehicle or thyroid hormones, which permitted the control of plasma thyroid hormone concentrations. The activity and expression of family 1 UGTs are correlated and were significantly modified by both thyroid status and amounts of retinol in the diet. Dietary vitamin A did not perturbe the UGT1A expression in thyroidectomized animals. Thyroid hormones and dietary vitamin A did not affect the activity and expression of family 2 UGTs. We conclude that thyroid hormones and vitamin A are co-regulator of the UGT1 family expression, without affecting the UGT2 family; by modifying activity and expression of the bilirubin UOT isoform, a member of UGT1 family, thyroid hormone reduced the glucuronidation of T4 and rT3.