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.
Haberkorn
Valérie
V
Unité de Biochimie-Pharmacologie-Toxicologie, EA/MENRT 2980 UFR Pharmacie, Université de Bourgogne, 7 Bd. Jeanne d'Arc, BP 87900, 21079 Dijon, France. valeriehaberkorn@hotmail.com
Heydel
Jean-Marie
JM
Mounie
Jacques
J
Artur
Yves
Y
Goudonnet
Hervé
H
D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D004032:Diet; D015971:Gene Expression Regulation, Enzymologic; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000201:enzymology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009284:Naphthols / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000378:metabolism*; D013965:Thyroidectomy; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000378:metabolism; D014801:Vitamin A / Q000008:administration & dosage / Q000378:metabolism*; D000099237:UDP-Galactose Translocators; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D014453:Glucuronosyltransferase; D009004:Monosaccharide Transport Proteins; D009284:Naphthols; D013963:Thyroid Hormones; D013974:Thyroxine; D014284:Triiodothyronine; D014801:Vitamin A; D000099237:UDP-Galactose Translocators; D000099148:UGT1A1 Enzyme; C499946:Ugt1a1 protein, rat