Effect of thyroid hormone on uncoupling protein-3 mRNA expression in rat heart and skeletal muscle.
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 beta-adrenergic systems. Hyperthyroidism was produced by three injections of 100 microg T3/100 g body weight on alternate days with or without concomitant treatment with either captopril (an angiotensin-converting enzyme [ACE] inhibitor), propranolol (a beta-blocker) or clenbuterol (a beta2-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 beta-adrenergic system and probably reflects a direct action of the hormone on UCP-3 gene expression.
Queiroz
Marcia Silva
MS
Department of Medicine and of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4951, USA.
Shao
Yvonne
Y
Ismail-Beigi
Faramarz
F
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002976:Clenbuterol / Q000494:pharmacology; D004357:Drug Synergism; D006980:Hyperthyroidism / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D007473:Ion Channels; D008297:Male; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000494:pharmacology*; D000071247:Uncoupling Protein 3
D000318:Adrenergic beta-Agonists; D000959:Antihypertensive Agents; D002352:Carrier Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D014284:Triiodothyronine; D002216:Captopril; D011433:Propranolol; D002976:Clenbuterol