TY - JOUR
T1 - Thyroid hormone signaling in male mouse skeletal muscle is largely independent of D2 in myocytes
AU - Werneck-De-Castro, Joao P.
AU - Fonseca, Tatiana L.
AU - Ignacio, Daniele L.
AU - Fernandes, Gustavo W.
AU - Andrade-Feraud, Cristina M.
AU - Lartey, Lattoya J.
AU - Ribeiro, Marcelo B.
AU - Ribeiro, Miriam O.
AU - Gereben, Balazs
AU - Bianco, Antonio C.
N1 - Publisher Copyright:
© 2015 by the Endocrine Society.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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.
AB - 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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U2 - 10.1210/en.2015-1246
DO - 10.1210/en.2015-1246
M3 - Article
C2 - 26214036
AN - SCOPUS:84943597432
SN - 0013-7227
VL - 156
SP - 3842
EP - 3852
JO - Endocrinology
JF - Endocrinology
IS - 10
ER -