Clofibrate increases hepatic triiodothyronine (T3)- and thyroxine (T4)-glucuronosyltransferase activities and lowers plasma T3 and T4 concentrations in pigs.
In rats, clofibrate acts as a microsomal enzyme inducer and disrupts the metabolism of thyroid hormones by increasing hepatic glucuronidation of thyroxine. Whether similar effects occur in the pig has not yet been investigated. This study was performed to investigate the effect of clofibrate treatment on metabolism of thyroid hormones in pigs. To this end, an experiment with 18 pigs, which were assigned to two groups, was performed. One group received a control diet, and the other group was fed the same diet supplemented with 5 g of clofibrate/kg for 28 days. Pigs treated with clofibrate had higher hepatic activities of T(3)- and T(4)-UDP glucuronosyltransferases (UGT) and lower concentrations of total and free T(4) and total T(3) in plasma than control pigs (P < 0.05). Weights and histology of the thyroid gland (epithelial height, follicle lumen diameter) did not differ between the two groups, but pigs treated with clofibrate had higher mRNA concentrations of various genes in the thyroid responsive to thyroid-stimulating hormone (TSH) such as TSH receptor, sodium iodine symporter, thyroid peroxidase, and cathepsin B than control pigs (P < 0.05). Pigs treated with clofibrate also had lower hepatic mRNA concentrations of proteins involved in plasma thyroid hormone transport [thyroxine-binding globulin (P < 0.10), transthyretin (P < 0.05), and albumin (P < 0.05)] and thyroid hormone receptor alpha(1) (P < 0.05) than control pigs. In conclusion, this study shows that clofibrate treatment induces a strong activation of T(3)- and T(4)-UGT in pigs, leading to increased glucuronidation and markedly reduced plasma concentrations of these hormones, accompanied by a moderate stimulation of thyroid function.
Luci
Sebastian
S
Institut für Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Emil-Abderhalden-Str 26, Halle/S, Germany.
Kluge
Holger
H
Hirche
Frank
F
Eder
Klaus
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002994:Clofibrate / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists; D013552:Swine; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood* / Q000378:metabolism
D000960:Hypolipidemic Agents; D047493:PPAR alpha; D014284:Triiodothyronine; C117189:thyroxine-UDP-glucuronosyltransferase; D014453:Glucuronosyltransferase; D002994:Clofibrate; D013974:Thyroxine