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

The beta -adrenergic system is very important in cardiovascular medicine. T hyroid hormone (T3) affects beta -adrenergic receptors, In cell culture, is oproterenol, a beta -adrenergic agonist, has been shown to upregulate thyro id hormone receptor (TR) mRNA, thus indicating a bi-directional regulation. The aim of this study was to evaluate if beta -adrenoreceptor blockade may affect subtype TR mRNA expression in vivo. Propranolol or vehicle was deli vered by implanting an Alzet osmotic pump subcutaneously in mice for 14d. T he concentration of TR alpha (1), alpha (2), beta (1) and beta (2) subtype mRNA concentrations were quantified by reverse transcription-polymerase cha in reaction and ELISA. Propranolol downregulated the levels of TR alpha (1) by 44% (p<0.0005) and <beta>(1) mRNA by 39% (p<0.0005) in mouse heart, in comparison to the contr ol, while no difference in the TR<alpha>(2) or beta (2) mRNA levels occurre d. The heart rate nas reduced by 10% (p<0.05) in the propranolol group, whe reas no reduction was detected in the control group. In mouse treated with propranolol serum, T3 levels were 21% lon;er, (p<0.05) while serum T3 level s were 23% higher (p<0.05) in comparison to the control. This is the first study suggesting that a <beta>-adrenoreceptor blockade su btype selectively regulates TR mRNA subtypes, thus giving us further knowle dge about the interaction between the beta -adrenergic system and the thyro id hormone sytem.