CARDIAC NUCLEAR HORMONE-RECEPTOR MESSENGER-RNA IN HEART-FAILURE IN MAN

Eight donor hearts and six explanted hearts due to dilated cardiomyopa thy, normal skeletal muscle and liver were analysed. Glucocorticoid re ceptor (GR) and thyroid hormone receptor (T3R) isoforms beta 1, beta 2 , alpha 1 and alpha 2 mRNA abundance were determined by solution hybri dization. Both GR and T3R receptor mRNA isoforms were lower in the myo cardium as compared to skeletal muscle and in particular to liver. GR mRNA abundance was higher than that of any T3R isoform while the sum o f ligand-binding isoforms (beta 1, beta 2 and alpha 1) were similar in the myocardium and in skeletal muscle as opposed to the liver where G R mRNA was higher. GR mRNA abundance was similar in right and left ven tricles from donor hearts and in cardiomyopathy. T3R beta 1 showed hig her levels in the right ventricle with higher levels in cardiomyopathy as compared to donor heart. T3R isoform alpha 1 and especially the al pha 1/alpha 2 ratio were lower in left ventricle in cardiomyopathy com pared to donor hearts. In conclusion, GR and T3R isoforms mRNA abundan ce are low in the human myocardium. In the failing myocardium GR and T 3R beta 2 and alpha 2 show no signs of reactivity while T3R beta 1 and alpha 1 mRNA adapt.