ROLE OF THYROID STATE ON INDUCTION BY CIPROFIBRATE OF LAURATE HYDROXYLASE AND PEROXISOMAL ENZYMES IN RAT-LIVER MICROSOMES

The effects of hypothyroidism and hyperthyroidism upon liver microsomal omega-laurate hydroxylase activity (cytochrome P450 IV A1-dependent), peroxisome proliferation marker enzyme activities and acyl CoA oxidase (AOX) expression induced by ciprofibrate (2 mg/kg/day during 8 days) were studied in the male Wistar rat so as to clarify firstly the possible involvement of thyroid hormones in the modification of peroxisomal ciprofibrate-induced enzyme activities in relation to hepatic microsomal cytochrome P450 IV A1 induction, and secondly the possible direct effect of thyroid hormones on the gene expression of specific peroxisomal enzymes. No significant change was found in the ciprofibrate-induced omega-laurate hydroxylase activity in hypothyroid rats or in rats that had received a large dose of triiodothyronine (LT3), suggesting that the thyroid hormone does not interfere with the peroxisome proliferation process through such an indirect mechanism. The induction by ciprofibrate [2-(4-(2-2dichlorocyclopropyl)phenoxyl-2methyl-propionic acid)] of mitochondrial alpha-glycerolphosphate dehydrogenase and microsomal bilirubin UDPGT was decreased about 3-fold and 1.5-fold, respectively, while the induction of peroxisomal AOX, carnitine acetyl transferase and enoyl CoA hydratase enzyme activities was decreased by 36%, 34% and 22% in thyroidectomized animals, as compared to euthyroid animals. However, no significant changes in the quantity of peroxisomal proteins and in the AOX mRNA level were noted. The administration of large doses of LT3 to normal rats decreased the peroxisomal ciprofibrate AOX enzyme induction with a marked concomitant decrease in the AOX mRNA level. This suggests that high doses of LT3 enhance the turnover of some specific mRNAs or down regulate the peroxisome proliferator receptor. Our results also do not exclude inhibition of catabolic activity towards AOX which depends on thyroid hormone.