Microsomal long-chain acyl-CoA thioesterase (carboxylesterase ES-4) is regulated by thyroxine.
Long chain acyl-CoA thioesterase activity is mainly located in microsomes after subcellular fractionation of liver from untreated rats. The physiological function and regulation of expression of this activity is not known. In the present study we have investigated the effect of thyroxine on expression of carboxylesterase ES-4, the major acyl-CoA thioesterase of liver microsomes. Thyroidectomy of rats decreased the palmitoyl-CoA thioesterase activity to about 25% of normal activity. This decrease was accompanied by similar decreases at the protein and mRNA levels (31% and 57%, respectively, of controls). Treatment with thyroxine completely reversed the effect of thyroidectomy and resulted in elevated levels in both thyroidectomized and control 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 thyroxine. ES-10 was not changed at the protein or mRNA level by any of the treatments, while ES-2 expression in liver was decreased by thyroxine treatment. The data shows that changes in activity and expression of ES-4 correlate to thyroxine status in the rat suggesting a physiological regulatory role by this hormone. Since thyroxine regulates the expression of lipogenic enzymes, 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.
Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, S-141 86, Huddinge, Sweden.
M A
MA
Diczfalusy
U
U
Andersson
I
I
Björkhem
C
C
Einarsson
S E
SE
Alexson
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010170:Palmitoyl-CoA Hydrolase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013965:Thyroidectomy; D013974:Thyroxine / Q000494:pharmacology*
D012333:RNA, Messenger; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D010170:Palmitoyl-CoA Hydrolase; D013974:Thyroxine