Hypothyroidism is associated with increased myostatin expression in rats.

Besides its key role in the regulation of muscle growth during development, myostatin also appears to be involved in muscle homeostasis in adults, and its expression is upregulated during muscle atrophy. Since muscle physiology is greatly influenced by thyroid status, and the myostatin promoter region contains several putative thyroid hormone response elements, in the present study we examined the possible role of thyroid hormones in the regulation of myostatin gene expression. Adult male rats were made either hypothyroid or hyperthyroid by means of administration of 0.1% amino- triazole (AMT) in drinking water for 4 weeks, or daily injections of Levo-T4 (L-T4) (100 microg/rat) for 3 weeks, respectively. At the end of the treatment period, both myostatin mRNA and protein content were increased in AMT-treated rats in relation to control rats. In contrast, no changes in myostatin mRNA levels were detected in L-T4-treated rats. The role of thyroid hormones in the regulation of myostatin expression was also investigated in C2C12 cells in vitro. Treatment of C2C12 cells with thyroid hormones stimulated their differentiation into multinucleated myotubes, but did not induce any change in myostatin mRNA abundance. In all, our findings demonstrate that myostatin expression is increased in hypothyroid rats, thus supporting a possible role for this factor in the pathogenesis of the muscle loss that may occur in hypothyroidism.