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) play an important regulatory role for in vivo and in vitro cardiac myosin heavy chain (MHC) isoform gene expression by activating the alpha- and inhibiting the beta-MHC genes. Previous studies have shown that chronic energy deprivation (CED; 50% of normal caloric intake) in the rat impacts cardiac MHC protein expression and hemodynamic parameters in a pattern typically seen with hypothyroidism; yet, unlike hypothyroidism, circulating T-3 levels are not depressed. Therefore, the goal of this study was to determine if the altered MHC isoform expression observed in CED is associated with altered TR expression, both at the mRNA and protein levels. Female rats weighing similar to 250 g were allocated into two groups, designated as normal control (NC) and CED. After 5 wk, the relative content of alpha-MHC protein and mRNA levels decreased in CED ventricles by 20% (P < 0.05). In contrast, the relative content 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 relative 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 of 840 +/- 130 fmol/mg DNA in NC to 241 +/- 118 fmol/mg DNA in CED, with no change in the affinity of the receptor. These data suggest that 1) MHC regulation appears to be controlled in CED at the pretranslational 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.