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


CONCLUSIONS
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.
Brennan
Michael D
MD
Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Coenen-Schimke
Jill M
JM
Bigelow
Maureen L
ML
Nair
K Sreekumaran
KS
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000596:Amino Acids / Q000097:blood; D001823:Body Composition; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy*; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D007700:Kinetics; D007930:Leucine / Q000097:blood; D009124:Muscle Proteins / Q000096:biosynthesis; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D010649:Phenylalanine / Q000097:blood; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D011868:Radioisotopes / Q000493:pharmacokinetics; D013974:Thyroxine / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000596:Amino Acids; D007457:Iodine Radioisotopes; D009124:Muscle Proteins; D012333:RNA, Messenger; D011868:Radioisotopes; D010649:Phenylalanine; D018995:Myosin Heavy Chains; D007930:Leucine; D013974:Thyroxine