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Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes
- Publication Year :
- 2015
- Publisher :
- Endocrine Society, 2015.
-
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 23 m/min; muscle strength was about 0.3 mN/m·g body weight in SKM-D2KO and control ankle muscles. In conclusion, there are multiple sources of D2 in the mouse SKM, and its role is limited in postnatal skeletal muscle fibers.
- Subjects :
- Male
medicine.medical_specialty
Thyroid Hormones
Myosin light-chain kinase
Time Factors
Deiodinase
Muscle Fibers, Skeletal
DIO2
Gene Expression
Mice, Transgenic
Tropomyosin
Iodide Peroxidase
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Endocrinology
Adipose Tissue, Brown
Internal medicine
Physical Conditioning, Animal
Myosin
medicine
Myocyte
Animals
Muscle Strength
Muscle, Skeletal
Cells, Cultured
Original Research
Mice, Knockout
biology
Myosin Heavy Chains
Reverse Transcriptase Polymerase Chain Reaction
Skeletal muscle
Thyroxine
medicine.anatomical_structure
Animals, Newborn
biology.protein
Triiodothyronine
MYH7
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....8ae0b90ecd73045b4c7008475b96b819