Protein Degradation in Skeletal Muscle during Experimental Hyperthyroidism in Rats and the Effect of β-Blocking Agents*

Abstract

beta-Blocking agents are increasingly used in the management of hyperthyroid patients. The effect of this treatment on increased muscle protein breakdown in the hyperthyroid state is not known. In the present study, experimental hyperthyroidism was induced in rats by daily ip injections of T3 (100 micrograms/100 g BW) during a 10-day period. Control animals received corresponding volumes of solvent. In groups of rats the selective beta-1-blocking agent metoprolol or the nonselective beta-blocker propranolol was infused by miniosmotic pumps implanted sc on the backs of the animals. Protein degradation was measured in incubated intact soleus and extensor digitorum longus muscles by determining tyrosine release into the incubation medium. The protein degradation rate in incubated extensor digitorum longus and soleus muscles was increased by 50-60% during T3 treatment. Metoprolol or propranolol did not influence muscle protein breakdown in either T3-treated or control animals. The results suggest that T3-induced increased muscle proteolysis is not mediated by beta-receptors, and muscle weakness and wasting in hyperthyroidism might not be affected by beta-blockers.

Effect of T3-induced hyperthyroidism on mitochondrial and cytoplasmic protein synthesis rates in oxidative and glycolytic tissues in rats

“…It has been shown in vitro (tyrosine release method) that the global breakdown rate of mixed proteins in diaphragm and hindlimb muscles is increased in young rats infused with T 3 for 4 -10 days in a process regulated through the proteosome pathway (1,33). Although muscle protein breakdown rate cannot be directly measured in vivo, the present study provides indirect support that tissue protein breakdown rate was increased in T 3 -treated rats.…”

“…Most animal studies showed that the mixed protein synthesis rate in skeletal muscle, liver, and heart is stimulated by excess thyroid hormone (1,3,8,9,16,23). In humans, whole body rates of protein synthesis and breakdown are increased in some (20,27,32,35) but not all (19,21) studies of hyperthyroid patients or short-term experimental hyperthyroidism.…”

“…Alterations in tissue protein content result from altered balance between protein synthesis and breakdown. Prior studies showed that elevated thyroid hormone levels results in increased protein synthesis and/or breakdown rates in skeletal muscle in humans (21,27) or heart (3,8,9,16), liver (23), or skeletal muscle (1,8) of animals. However, it remains to be determined whether these changes noted for mixed protein synthesis represent similar directional changes in all tissue proteins.…”

Quantification of hormone-induced atrophy of large myotubes from C2C12 and L6 cells: atrophy-inducible and atrophy-resistant C2C12 myotubes

“…Microarray analysis of glucocorticoid-induced myopathy in vivo was described recently (13). Proteolysis is also enhanced in hyperthyroidism (1,4,7), explaining the body weight loss of thyrotoxic patients (20); but in contrast to glucocorticoids, thyroid hormones act as positive regulators of muscle development (9). Microarray analysis of 3,3Ј,5-triiodo-L-thyronine (T 3 )-treated human skeletal muscle confirmed the wide range of T 3 targets (5).…”

Effects of Diet and Metoprolol on Lípid Levels in the Blood Plasma and Morphology of the Heart and Intramural Branches of Coronary Arteries of Spontaneously Hypertensive Male Rats

“…In addition, me toprolol treatment also affected growth and food consumption in a way that may indi cate some interference with basal metabolic processes. This apparent increase in energy consumption was somewhat surprising, since p-adrenoceptor-blocking agents are currently used in the treatment of hyperthy roid patients [30], However, recent studies in rats have failed to demonstrate effects of Pi-blockade on some of the metabolic altera- tions induced by triiodothyronine treatment [31,32], It is not possible from the available data to decide neither what the type of dis turbance is underlying the effects of metoprolol on growth and food consumption, nor if the effects were due to the drug itself, or to its metabolite(s) [22,23],…”