Hypothyroidism is associated with increased myostatin expression in rats

Abstract

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.

Hypothyroidism decreases proinsulin gene expression and the attachment of its mRNA and eEF1A protein to the actin cytoskeleton of INS-1E cells

“…This differential modulation indicates that the presence of TH at physiological concentrations is essential for the establishment of some biological processes, as demonstrated by proinsulin mRNA expression. Indeed, these data agree with reports that showed an increase of myostatin gene expression in hypothyroid rats, even though no changes in myostatin mRNA levels were detected in L-T4-treated rats (31). However, the mechanisms underlying these alterations, observed only in the hypothyroid condition, are unknown.…”

Thyroid states regulate subcellular glucose phosphorylation activity in male mice

“…Another possibility is that prolonged T 3 treatment in cells is needed to achieve results similar to those observed in animal models. Of note, studies in which T 3 acute effect is not the aim usually perform treatments for no longer than 24 h (55, 56). …”

Myostatin as a Biomarker of Muscle Wasting and other Pathologies-State of the Art and Knowledge Gaps

“…A research on the 5’-terminal regulatory region of the myostatin gene revealed various agents possibly acting as transcriptional factors, such as myocyte enhancing factor 2 (MEF2), peroxisome proliferator-activated receptor gamma (PPARγ), MyoD and NF-κB, as well as a mechanism for myostatin upregulation by glucocorticoids [ 62 ]. Myostatin gene expression was also found to be affected by tumor necrosis factor -α (TNF-α), hormones (such as insulin-like growth factor (IGF-1), angiotensin II and thyroid hormones), nutritional supplementation, hyperammonemia, physical exercise and hypoxia [ 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. Furthermore, myostatin was found to down-regulate its expression in a self-regulatory loop [ 71 ].…”