Microsomal long-chain acyl-CoA thioesterase (carboxylesterase ES-4) is regulated by thyroxine

Long chain acyl-CoA thioesterase activity is mainly located in microsomes a fter subcellular fractionation of liver from untreated rats. The physiologi cal function and regulation of expression of this activity is not known. In the present study we have investigated the effect of thyroxine on expressi on of carboxylesterase ES-4, the major acyl-CoA thioesterase of liver micro somes. Thyroidectomy of rats decreased the palmitoyl-Coh thioesterase activ ity to about 25% of normal activity. This decrease was accompanied by simil ar decreases at the protein and mRNA levels (31% and 57%, respectively, of controls). Treatment with thyroxine completely reversed the effect of thyro idectomy and resulted in elevated levels in both thyroidectomized and contr ol rats. For reasons of comparison we also studied the possibility that ES- 10 and ES-2, two other members of the same gene family, are affected by thy roxine. ES-10 was not changed at the protein or mRNA level by any of the tr eatments, while ES-2 expression in liver was decreased by thyroxine treatme nt. The data shows that changes in activity and expression of ES-4 correlat e to thyroxine status in the rat suggesting a physiological regulatory role by this hormone. Since thyroxine regulates the expression of lipogenic enz ymes, these results are consistent with a function for this microsomal acyl -CoA thioesterase in fatty acid synthesis and/or secretion, rather than in oxidative degradation of fatty acids. (C) 1999 Elsevier Science B.V. All ri ghts reserved.