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

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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.
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© 2015 by the Endocrine Society.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.
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Adipose Tissue, Brown , Animals , Animals, Newborn , Cells, Cultured , Gene Expression , Iodide Peroxidase , Male , Mice, Knockout , Mice, Transgenic , Muscle Fibers, Skeletal , Muscle Strength , Muscle, Skeletal , Myosin Heavy Chains , Physical Conditioning, Animal , Reverse Transcriptase Polymerase Chain Reaction , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Signal Transduction , Thyroid Hormones , Thyroxine , Time Factors , Triiodothyronine , Tropomyosin
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