2015
DOI: 10.1210/en.2015-1246
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Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes

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… Show more

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Cited by 23 publications
(44 citation statements)
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“…This suggestion is reinforced by D2KO myogenesis data; these mice had impaired muscle development after birth and reduced regeneration (Dentice et al 2010). However, downregulation of muscular D2 in adult mice did not impair muscle function or T 3 signalling (Werneck-de-Castro et al 2015). Furthermore, T 3 stimulation of myoblast differentiation involves the inhibition of AP1, an inhibitor of differentiation, via THRa ( Fig.…”
Section: Thyroid Hormone Impact On Myogenesismentioning
confidence: 90%
See 1 more Smart Citation
“…This suggestion is reinforced by D2KO myogenesis data; these mice had impaired muscle development after birth and reduced regeneration (Dentice et al 2010). However, downregulation of muscular D2 in adult mice did not impair muscle function or T 3 signalling (Werneck-de-Castro et al 2015). Furthermore, T 3 stimulation of myoblast differentiation involves the inhibition of AP1, an inhibitor of differentiation, via THRa ( Fig.…”
Section: Thyroid Hormone Impact On Myogenesismentioning
confidence: 90%
“…However, global D2KO mice have normal levels of T 3 and increased levels of T 4 and TSH (Schneider et al 2001). Moreover, knockdown of muscular D2 by approximately 40-50% during muscle development or after muscle fibre differentiation does not significantly change TH serum levels (Werneck-de-Castro et al 2015, Ignacio et al 2017. Although it is important to note that despite normal TH serum levels, D2KO mice present a reduction in SM T 3 levels and a hypothyroid muscle phenotype (Schneider et al 2001, Bárez-López et al 2014.…”
Section: Thyroid Hormone and Skeletal Muscle Physiologymentioning
confidence: 99%
“…The fact that skeletal muscle physiology is T 3 -sensitive (46) sets the stage for a potential D2 contribution, such as during development and response to injury (47). Nevertheless, selective D2 inactivation in the mouse skeletal muscle failed to identify a metabolic phenotype, and serum T 3 was preserved due to increased thyroidal T 3 production (48,49). The present findings are particularly relevant because the thyroid gland does not adjust T 3 production during fasting (8), and serum T 3 drops also as a consequence of FOXO1-mediated DIO2 inhibition.…”
Section: Discussionmentioning
confidence: 99%
“…; Werneck‐de‐Castro et al . ). The GLOB‐D2KO mice exhibit impaired muscle regeneration after cardiotoxin‐induced injury, attributed to a reduction in T 3 signalling, and cultures of skeletal myocytes obtained from this mouse exhibited a phenotype of excessive proliferation and impaired differentiation (Dentice et al .…”
Section: Introductionmentioning
confidence: 97%
“…The SKM‐D2KO mouse lacks D2 in the later phases of muscle differentiation, and during adulthood only a mild tissue hypothyroidism is observed in basal states (Werneck‐de‐Castro et al . ). In addition, both exercise capacity and muscle function are preserved in the SKM‐D2KO mouse, a model that lends itself to physical exercise studies (Werneck‐de‐Castro et al .…”
Section: Introductionmentioning
confidence: 97%