Myocardial retinoid X receptor, thyroid hormone receptor, and myosin heavychain gene expression in the rat during adult aging

Although previous studies have shown that cardiac myosin heavy chain (MHC) composition undergoes a switch from the alpha- to beta-isoform in the heart during adult aging, the underlying mechanisms responsible for this switch are unknown. Cardiac MHC gene expression is regulated, in part, by thyroid hormone responsive elements present in the regulatory control regions of th e alpha- and beta-MHC genes. Age-associated changes in the expression of th yroid hormone receptors (THRs) and/or retinoid X receptors (RXRs) the heter odimeric partner for THRs, could explain the age-associated changes in MHC expression. Accordingly, we measured mRNA levels for the cardiac muscle MHC s and the rat THR and RXR genes in the left ventricles of Wistar rats at 2, 6 and 24 months of age. Although there were no significant changes in RXR alpha or RXR beta mRNA levels with age, both alpha 1 and alpha 2 THR mRNA l evels decreased significantly between 2 and 6 months of age. During this sa me time period, the mRNA levels for alpha-MNC declined by more than half; w hereas beta-MHC mRNA levels remained low and unchanged. On the other hand, between 6 and 24 months, when mRNA levels for beta-MHC increased and alpha- MHC continued to decrease, there was a significant decline in THR beta 1 an d RXR gamma mRNA levels accompanied by a reduction in the THR beta 1 and RX R gamma protein levels. These data show a pattern of change that suggests t hat Be decline in alpha-MHC gene expression may be biphasic and due to a de cline in alpha 1 (and possibly alpha 2) THR levels between 2 and 6 months o f age and a decline in THR beta 1 and RXR gamma levels at later stages. In contrast the increase in beta-MHC gene expression was associated only with the changes in THR beta 1 and RXR gamma mRNA and protein levels.