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Cited by 89Muscle Physiology and DisordersThyroid Disorders and TreatmentsAdipose Tissue and Metabolism

Effects of thyroid hormone receptor gene disruption on myosin isoform expression in mouse skeletal muscles

Yu, Fushun, Göthe, Sten, Wikström, Lilian, Forrest, Douglas, Vennström, Björn, Larsson, Lars·2000·American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
DOI 10.1152/ajpregu.2000.278.6.r1545
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Abstract

Skeletal muscle is known to be a target for the active metabolite of thyroid hormone, i.e., 3,5,3′-triiodothyronine (T 3). T 3 acts by repressing or activating genes coding for different myosin heavy chain (MHC) isoforms via T 3 receptors (TRs). The diverse function of T 3 is presumed to be mediated by TR-α 1 and TR-β, but the function of specific TRs in regulating MHC isoform expression has remained undefined. In this study, TR-deficient mice were used to expand our knowledge of the mechanisms by which T 3 regulates the expression of specific MHC isoforms via distinct TRs. In fast-twitch extensor digitorum longus (EDL) muscle, TR-α 1-, TR-β-, or TR-α 1 β-deficient mice showed a small but statistically significant decrease ( P < 0.05) of type IIB MHC content and an increased number of type I fibers. In the slow-twitch soleus, the β/slow MHC (type I) isoform was significantly ( P < 0.001) upregulated in the TR-deficient mice, but this effect was highly dependent on the type of receptor deleted. The lack of TR-β had no significant effect on the expression of MHC isoforms. An increase ( P < 0.05) of type I MHC was observed in the TR-α 1-deficient muscle. A dramatic overexpression ( P < 0.001) of the slow type I MHC and a corresponding downregulation of the fast type IIA MHC ( P < 0.001) was observed in TR-α 1 β-deficient mice. The muscle- and fiber-specific differences in MHC isoform expression in the TR-α 1 β-deficient mice resembled the MHC isoform transitions reported in hypothyroid animals, i.e., a mild MHC transition in the EDL, a dramatic but not complete upregulation of the β/slow MHC isoform in the soleus, and a variable response to TR deficiency in different soleus muscle fibers. Thus the consequences on muscle are similar in the absence of thyroid hormone or absence of thyroid hormone receptors, indicating that TR-α 1 and TR-β together mediate the known actions of T 3. However, it remains unknown how thyroid hormone exerts muscle- and muscle fiber-specific effects in its action. Finally, although developmental MHC transitions were not studied specifically in this study, the absence of embryonic and fetal MHC isoforms in the TR-deficient mice indicates that ultimately the transition to the adult MHC isoforms is not solely mediated by TRs.

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Crossref · 10.1152/ajpregu.2000.278.6.r1545

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  • UCP3 increases in skeletal muscle of mice during acute sepsis and inflammation as well as in skeletal muscle of NTIS patients, coinciding with increased DIO2 expression.

    “UCP3, which is a T3 target gene, increases in skeletal muscle of mice during acute sepsis [42] and inflammation [43] as well as in skeletal muscle of NTIS patients, coinciding with increased DIO2 expression [44].”

    From An update on non-thyroidal illness syndrome (2021) · cites this paper as [43]

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Authors
Yu, F., Göthe, S., Wikström, L., Forrest, D., Vennström, B., & Larsson, L.
Affiliations
  • Pennsylvania State University (US)
  • Karolinska Institutet (SE)
  • Icahn School of Medicine at Mount Sinai (US)
ORCID
Venue
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Publisher
American Physiological Society
Published
2000-06-01
Volume
278
Issue
6
Pages
R1545-R1554
ISSN
  • 0363-6119 (ISSN-L)
  • 1522-1490
DOI
10.1152/ajpregu.2000.278.6.r1545
OpenAlex
W1942265307
Cited by
89
References
35
Citations by year
2024: 3 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 11 · 2016: 2 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 3
FWCI
1.93
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
thyroid hormone receptor, myosin heavy chain isoforms, triiodothyronine, skeletal muscle, extensor digitorum longus, soleus muscle, hypothyroidism, gene disruption, muscle fiber type
MeSH terms
Adenosine Triphosphatases, Animals, Cell Count, Electrophoresis, Female, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Organ Size, Receptors, Thyroid Hormone, Thyroxine, Gene Expression, Mice, Knockout, Muscle, Skeletal, Muscle Fibers, Fast-Twitch, Muscle Fibers, Slow-Twitch, Myosin Heavy Chains, Cell Size, Mice

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