EFFECT OF CHRONIC ENERGY DEPRIVATION ON CARDIAC THYROID-HORMONE RECEPTOR AND MYOSIN ISOFORM EXPRESSION

Thyroid hormone (3,5,3'-triiodothyronine; T-3) and its receptor (TR) p lay an important regulatory role for in vivo and in vitro cardiac myos in heavy chain (MHC) isoform gene expression by activating the alpha- and inhibiting the beta-MHC genes. Previous studies have shown that ch ronic energy deprivation (CED; 50% of normal caloric intake) in the ra t impacts cardiac MHC protein expression and hemodynamic parameters in a pattern typically seen with hypothyroidism; yet, unlike hypothyroid ism, circulating T-3 levels are not depressed. Therefore, the goal of this study was to determine if the altered MHC isoform expression obse rved in CED is associated with altered TR expression, both at the mRNA and protein levels. Female rats weighing similar to 250 g were alloca ted into two groups, designated as normal control (NC) and CED. After 5 wk, the relative content of alpha-MHC protein and mRNA levels decrea sed in CED ventricles by 20% (P < 0.05). In contrast, the relative con tent of both p-MHC protein and mRNA levels increased five- to sixfold in CED (P < 0.05). Although there were no changes in TR mRNA levels re lative to 18S rRNA in CED, the total number of nuclear TRs decreased 3 .5-fold in the CED group (P < 0.05), from a maximum binding capacity o f 840 +/- 130 fmol/mg DNA in NC to 241 +/- 118 fmol/mg DNA in CED, wit h no change in the affinity of the receptor. These data suggest that 1 ) MHC regulation appears to be controlled in CED at the pretranslation al level; 2) the increase in beta-MHC expression and decrease in alpha -MHC expression are associated with a decrease in TR protein content, i.e., those proteins involved with beta-MHC transcriptional repression and alpha-MHC gene activation; and 3) the regulation of TR expression in the heart during CED appears to be at either the translational and /or the posttranslational level.