Subtype Specific Downregulation of Thyroid Hormore Receptor mRNA by β-Adrenoreceptor Blockade in the Myocardium

概要

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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 14d. The concentration of TRα_1,α_2,β_1 and β_2 subtype mRNA concentrations were quantified by reverse transcription-polymerase chain reaction and ELISA.Propranolol downregulated the levels of TRα_1 by 44% (p<0.0005) and β_1 mRNA by 39% (p<0.0005) in mouse heart, in comparison to the control, while no difference in the TRα_2 or β_2 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.
公益社団法人日本薬学会の論文
2000-11-01