Changes in skeletal muscle protein metabolism and myosin heavy chain isoform messenger ribonucleic acid abundance after treatment of hyperthyroidism

Michael D. Brennan, Jill M. Coenen-Schimke, Maureen L. Bigelow, K. Sreekumaran Nair

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Background: Hyperthyroidism causes a hypermetabolic state and skeletal muscle dysfunction, but the underlying mechanism remains incompletely defined. Objective: The objective of the study was to determine whether treatment of hyperthyroidism causes changes in amino acid fluxes, synthesis rates of muscle proteins, and expression of muscle myosin heavy chain (MHC) that may impact skeletal muscle function and metabolic rate. Methods: Eight hyperthyroid patients were studied (TSH 0.008 ± 0.001 mU/liter) before treatment and at least 9 months after correction of hyperthyroidism (TSH 2.3 ± 0.4) (P < 0.03). Fluxes of leucine and phenylalanine as well as muscle protein synthesis rates were measured using L[1,2 13C] leucine and L( 15N) phenylalanine as tracers. mRNA levels of selected genes were measured in muscle biopsy samples. Results: Treatment decreased resting metabolic rate that paralleled changes in fluxes of leucine and phenylalanine accompanied by improved muscle strength and mass. Synthesis rates of mixed muscle proteins (P = 0.01), sarcoplasmic (P = 0.04), and mitochondrial (P = 0.08) proteins decreased, whereas MHC synthesis was unchanged. Selective increases in mRNA abundance of muscle MHC1 isoform (P = 0.04) and decrease of MHCIIA (P = 0.007) and MHCIIx (P = 024) were observed. Muscle mitochondrial oxidative enzymes and mRNA levels of mitochondrial proteins were unchanged, but uncoupling protein2 and uncoupling protein3 mRNA levels (P = 0.02) decreased. Conclusion: Increased amino acid flux, mixed muscle protein synthesis, and synthesis of sarcoplasmic proteins are consistent with the hypermetabolic state in hyperthyroidism. After treatment, MHC synthesis rates were unchanged, but mRNA levels of isoforms of MHC found in slow-twitch and fast-twitch fibers increased and decreased, respectively. These results offer a mechanistic explanation for posttreatment improvement in muscle functions in hyperthyroidism.

Original languageEnglish (US)
Pages (from-to)4650-4656
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Issue number11
StatePublished - Nov 2006

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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