Dysregulated Thyroid Hormone Metabolism Following Formoterol Stimulation In Thyroid Hormone Depleted Skeletal Muscle

Abstract

In skeletal muscle (SKM), signal transduction of thyroid hormone (TH) exerts subcellular downstream effects by influencing mechanisms of gene expression. People with hypothyroidism commonly experience SKM pain, fatigue, and intolerance to exercise, which may be driven by dysregulated TH metabolism. PURPOSE: To use an in vitro model of hypothyroidism to test the hypothesis that SKM cells will have dysregulated TH metabolism. Additionally, the exercise mimetic, formoterol, was used to determine the effects of exercise signaling on TH depleted cells. METHODS: Human SKM myoblasts (n = 6 per group) were cultured and differentiated until mature myotube formation (Day 6). Groups included control cells (CON), TH depleted cells (ThD), and TH depleted cells plus formoterol stimulation (ThD+F; 30nM for 3h). Total RNA was extracted during mid-myogenesis (Day 4) and at terminal differentiation (Day 6). Gene expression for Thyroid Hormone Receptor Alpha (THRα), Deiodinase 2 (DIO2), and Deiodinase 3 (DIO3) was determined by qPCR. Data were analyzed by repeated measures ANOVA. RESULTS: Significant differences between conditions and time points are detailed in Table 1. CONCLUSION: THRα was reduced by ThD and further decreased by ThD+F, suggesting that the combination of ThD+F is highly suppressive of this receptor. Intracellular activation of TH (T3) by DIO2 stimulates nuclear transcripts leading multiple cellular functions. Formoterol stimulation increased DIO2 but was decreased in the ThD group, indicating a potential lower availability of T3. Interestingly, DIO3 was also increased by formoterol stimulation, which could counteract availability of T3 via conversion to reverse T3. More research addressing hypothyroidism and exercise is warranted as there may be negative consequences regarding exercise mode and intensity. This work was supported by a Texas ACSM SRDA grant.Table 1