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. Thyroid hormone (T3) affects beta-adrenergic receptors. In cell culture, isoproterenol, a beta-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 beta-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 TRalpha1, alpha2, beta1 and beta2 subtype mRNA concentrations were quantified by reverse transcription-polymerase chain reaction and ELISA. Propranolol downregulated the levels of TRalpha1 by 44% (p < 0.0005) and beta1 mRNA by 39% (p < 0.0005) in mouse heart, in comparison to the control, while no difference in the TRalpha2 or beta2 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 beta-adrenoreceptor blockade subtype selectively regulates TR mRNA subtypes, thus giving us further knowledge about the interaction between the beta-adrenergic system and the thyroid hormone sytem.
Shahrara
S
S
Department of Cardiology, Karolinska Institute, Huddinge Hospital, S-14186 Stockholm, Sweden.
Sylvén
C
C
Drvota
V
V
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects*; D004562:Electrocardiography / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D012313:RNA; D012333:RNA, Messenger / Q000096:biosynthesis*; D012339:RNA, Ribosomal, 28S / Q000096:biosynthesis / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis*; D012015:Reference Standards; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D000319:Adrenergic beta-Antagonists; C034477:RNA primers; D012333:RNA, Messenger; D012339:RNA, Ribosomal, 28S; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D012313:RNA; D011433:Propranolol; D013974:Thyroxine