RESUMO
BACKGROUND/AIMS: Thyroid hormone (TH) signalling is critical for heart function. The heart expresses thyroid hormone receptors (THRs); THRα1 and THRß1. We aimed to investigate the regulation mechanisms of the THRß isoform, its association with gene expression changes and implications for cardiac function. METHODS: The experiments were performed using adult male mice expressing TRßΔ337T, which contains the Δ337T mutation of the human THRB gene and impairs ligand binding. Cardiac function and RNA expression were studied after hypo-or hyperthyroidism inductions. T3-induced cardiac hypertrophy was not observed in TRßΔ337T mice, showing the fundamental role of THRß in cardiac hypertrophy. RESULTS: We identified a group of independently regulated THRß genes, which includes Adrb2, Myh7 and Hcn2 that were normally regulated by T3 in the TRßΔ337T group. However, Adrb1, Myh6 and Atp2a2 were regulated via THRß. The TRßΔ337T mice exhibited a contractile deficit, decreased ejection fraction and stroke volume, as assessed by echocardiography. In our model, miR-208a and miR-199a may contribute to THRß-mediated cardiac hypertrophy, as indicated by the absence of T3-regulated ventricular expression in TRßΔ337T mice. CONCLUSION: THRß has important role in the regulation of specific mRNA and miRNA in T3-induced cardiac hypertrophic growth and in the alteration of heart functions.