TRs have common and isoform-specific functions in regulation of the cardiac myosin heavy chain genes

TR alpha1 and TR beta mediate the regulatory effects of T-3 and have profou nd effects on the cardiovascular system. We have analyzed the expression of the cardiac myosin heavy chain (MyHC) genes alpha and beta in mouse strain s deficient for one or several TR genes to identify specific regulatory fun ctions of TR alpha1 and TR beta. The results show that TR alpha1 deficiency , which slows the heart rate, causes chronic overexpression of MyHC beta. H owever, MyHC beta was still suppressible by T. in both TR alpha1- and TR be ta -deficient mice, indicating that either receptor can mediate repression of MyHC beta. T-3-dependent induction of the positively regulated MyHC alph a gene was similar in both TR alpha1 and TR beta -deficient mice. The data identify a specific role for TR alpha1 in the negative regulation of MyHC b eta, whereas TR alpha1 and TR beta appear interchangeable for hormone-depen dent induction of MyHC alpha. This suggests that TR isoforms exhibit distin ct specificities in the genes that they regulate within a given tissue type . Thus, dysregulation of MyHC beta is likely to contribute to the critical role of TR alpha1 in cardiac function.