Thyroid hormone signaling in male mouse skeletal muscle is largely independent of D2 in myocytes

Joao P. Werneck-De-Castro, Tatiana L. Fonseca, Daniele L. Ignacio, Gustavo W. Fernandes, Cristina M. Andrade-Feraud, Lattoya J. Lartey, Marcelo B. Ribeiro, Miriam O. Ribeiro, Balazs Gereben, Antonio C. Bianco

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Abstract

The type 2 deiodinase (D2) activates the prohormone T4 to T3.D2 is expressed in skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly leads to skeletal muscle hypothyroidism and impaired differentiation. Here floxed Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin light chain 1f (cre-MLC) to disrupt D2 expression in the late developmental stages of skeletal myocytes (SKM-D2KO). This led to a loss of approximately 50% in D2 activity in neonatal and adult SKM-D2KO skeletal muscle and about 75% in isolated SKM-D2KO myocytes. To test the impact of Dio2 disruption, we measured soleus T3 content and found it to be normal. We also looked at the expression of T3-responsive genes in skeletal muscle, ie, myosin heavy chain I, α-actin, myosin light chain, tropomyosin, and serca 1 and 2, which was preserved in neonatal SKM-D2KO hindlimb muscles, at a time that coincides with a peak of D2 activity in control animals. In adult soleus the baseline level of D2 activity was about 6-fold lower, and in the SKM-D2KO soleus, the expression of only one of five T3-responsive genes was reduced. Despite this, adult SKM-D2KO animals performed indistinguishably from controls on a treadmill test, running for approximately 16 minutes and reached a speed of about 23m/min;musclestrengthwasabout0.3mN/m-gbodyweightinSKM-D2KOandcontrolanklemuscles. In conclusion, there are multiple sources of D2 in the mouse SKM, and its role is limited in postnatal skeletal muscle fibers.

Original languageEnglish
Pages (from-to)3842-3852
Number of pages11
JournalEndocrinology
Volume156
Issue number10
DOIs
Publication statusPublished - Oct 1 2015

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ASJC Scopus subject areas

  • Endocrinology

Cite this

Werneck-De-Castro, J. P., Fonseca, T. L., Ignacio, D. L., Fernandes, G. W., Andrade-Feraud, C. M., Lartey, L. J., Ribeiro, M. B., Ribeiro, M. O., Gereben, B., & Bianco, A. C. (2015). Thyroid hormone signaling in male mouse skeletal muscle is largely independent of D2 in myocytes. Endocrinology, 156(10), 3842-3852. https://doi.org/10.1210/en.2015-1246