Subtype specific downregulation of thyroid hormone receptor mRNA by β-adrenoreceptor blockade in the myocardium

Abstract

The β-adrenergic system is very important in cardiovascular medicine. Thyroid hormone (T3) affects β-adrenergic receptors. In cell culture, isoproterenol, a β-adrenergic agonist, has been shown to upregulate thyroid hormone receptor (TR) mRNA, thus indicating a bi-directional regulation. The aim of this study was to evaluate if β-adrenoreceptor blockade may affect subtype TR mRNA expression in vivo. Propranolol or vehicle was delivered by implanting an Alzet osmotic pump subcutaneously in mice for 14 d. The concentration of TRα1, α2, β1 and β2 subtype mRNA concentrations were quantified by reverse transcription-polymerase chain reaction and ELISA. Propranolol downregulated the levels of TRα1 by 44% (p<0.0005) and β1 mRNA by 39% (p<0.0005) in mouse heart, in comparison to the control, while no difference in the TRα2 or β2 mRNA levels occurred. The heart rate was reduced by 10% (p<0.05) in the propranolol group, whereas no reduction was detected in the control group. In mouse treated with propranolol serum, T3 levels were 21% lower, (p<0.05) while serum T4 levels were 23% higher (p<0.05) in comparison to the control. This is the first study suggesting that a β-adrenoreceptor blockade subtype selectively regulates TR mRNA subtypes, thus giving us further knowledge about the interaction between the β-adrenergic system and the thyroid hormone sytem.