Thyroid Hormones and Skeletal Muscle Beyond Thermogenesis

Abstract

Thyroid hormones are widely studied for their involvement in energy metabolism and thermogenesis. However, their role on muscle fibers and the structure and organelles of this tissue has yet to be reviewed. This mini-review aims to show the involvement of thyroid hormone signalings in the function of muscle fibers. Serum levels of thyroid hormones depend on the hypothalamic–pituitary–thyroid axis, which, in turn, acts depending on changes in homeostasis and the environment. In skeletal muscle, thyroxine (T4) and triiodothyronine (T3) participate in contractile function, metabolism, myogenesis, and regeneration. T3 regulates skeletal muscle gene expression through the interaction with the specific nuclear isoforms receptors for thyroid hormones: α (THRA) and β (THRB). In addition, T3 activates phosphoinositide 3-kinase (PI3K), which ultimately increases the transcription of hypoxia-inducible factor 1-alpha (HIF-1α). They can bind to a membrane integrin, Alpha-5 beta-3 integrin (αvβ3), and activate the PI3K and mitogen-activated protein kinase (MAPK) signal transduction pathways. T3 and T4 also increase Fibroblast Growth Factor 2 (FGF2) gene transcription. These initially nongenomic, nonclassical actions serve as additional interfaces for transcriptional regulation by thyroid hormones. In addition, di-iodine (T2), the thyroid hormone metabolite, has been shown to play a role in this process.

Keywords

TSH / T3 / T4 / Myogenesis / Skeletal muscle

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