Hypothyroidism and skeletal muscle: An in vitro model of investigating impaired pathways of muscle health



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Hypothyroidism is a prevalent metabolic condition in the United States primarily affecting women. Individuals treated for hypothyroidism commonly report symptoms including skeletal muscle (SKM) pain, fatigue and intolerance to exercise even while under treatment. Exercise is an alternate intervention with potential benefits offsetting hypothyroidism due to overlapping thyroid hormone and exercise signaling pathways. The purpose of the study was to investigate the effects of hypothyroidism on SKM metabolism, myogenesis, mitochondria and cellular homeostasis and assess whether an exercise intervention could reduce the detriments caused by intracellular low thyroid hormone availability. An in vitro human SKM cell culture low availability of thyroid hormone model was utilized to represent hypothyroidism. The exercise mimetic, formoterol, was used to provide “exercise” stimulation. This experiment was conducted during the mid- and late stages of myogenesis. The model included three conditions (n = 6), control (CON), thyroid hormone depleted (ThD), and thyroid hormone depleted with three-hour acute formoterol treatment (ThD+F). Skeletal muscle myocytes were differentiated for four or six days in low thyroid hormone media with the ThD+F group stimulated with formoterol for three hours. Extraction of total RNA was performed on days four and six followed by qPCR for gene analysis. Gene expression was assessed for the following categories: (a) thyroid hormone metabolism, (b) myogenesis, (c) mitochondrial homeostasis, and (d) cellular homeostasis. The  CT method was used to normalize the data followed by two-way repeated measures ANOVA. Significance was set at p < .05. The low availability of thyroid hormone and formoterol treatment significantly impacted the expression of genes related to thyroid hormone metabolism, myogenesis, mitochondrial homeostasis, and cellular homeostatic function in skeletal muscle cells. The intracellular low thyroid hormone availability was compounded by the formoterol treatment leading to decreases in gene expression associated with myogenesis, reactive oxygen species mediation, and metabolism in the skeletal muscle myocytes. Exercise may cause deleterious effects on skeletal muscle in individuals with hypothyroidism. Further research is warranted to determine the safety and prescription of exercise for those with hypothyroidism.



Hypothyroidism, Exercise, Gene transcription