Effect of Thyroid Hormone on Uncoupling Protein-3 mRNA Expression in Rat Heart and Skeletal Muscle

Abstract

Thyroid hormones (triiodothyronine [T₃] and thyroxine [T₄]) stimulate UCP-3 expression in skeletal muscle. We examined whether thyroid hormone-induced changes in uncoupling protein(UCP)-3 mRNA expression are related to directs effects of T₃ or reflect secondary effects of the hormone through stimulation of renin-angiotensin or β-adrenergic systems. Hyperthyroidism was produced by three injections of 100 μg T₃/100 g body weight on alternate days with or without concomitant treatment with either captopril (an angiotensin-converting enzyme [ACE] inhibitor), propranolol (a β-blocker) or clenbuterol (a β ₂-agonist). The relative abundance of UCP-3 mRNA was measured in ventricular myocardium and skeletal muscle (gastrocnemius and soleus). T₃ resulted in a significant increase in the relative abundance of UCP-3 in heart and skeletal muscle (p < 0.05), and the effect was not altered by captopril or propanolol; the inhibitors alone had no effect of UCP-3 mRNA content. There was no synergistic or additive effect of T₃ and clenbuterol on UCP-3 mRNA expression in skeletal muscle. Increased UCP-3 mRNA levels were associated with increased UCP-3 protein expression in skeletal muscle. We conclude that the effect of T₃ on UCP-3 expression in cardiac and skeletal muscle is not dependent on either angiotensin II or the β-adrenergic system and probably reflects a direct action of the hormone on UCP-3 gene expression.