In:
Endocrinology, The Endocrine Society, Vol. 151, No. 12 ( 2010-12-01), p. 5952-5960
Abstract:
Because of its large mass, relatively high metabolic activity and responsiveness to thyroid hormone, skeletal muscle contributes significantly to energy expenditure. Despite the presence of mRNA encoding the type 2 iodothyronine-deiodinase (D2), an enzyme that activates T4 to T3, very low or undetectable activity has been reported in muscle homogenates of adult humans and mice. With a modified D2 assay, using microsomal protein, overnight incubation and protein from D2 knockout mouse muscle as a tissue-specific blank, we examined slow- and fast-twitch mouse skeletal muscles for D2 activity and its response to physiological stimuli. D2 activity was detectable in all hind limb muscles of 8- to 12-wk old C57/BL6 mice. Interestingly, it was higher in the slow-twitch soleus than in fast-twitch muscles (0.40 ± 0.06 vs. 0.076 ± 0.01 fmol/min · mg microsomal protein, respectively, P & lt; 0.001). These levels are greater than those previously reported. Hypothyroidism caused a 40% (P & lt; 0.01) and 300% (P & lt; 0.001) increase in D2 activity after 4 and 8 wk treatment with antithyroid drugs, respectively, with no changes in D2 mRNA. Neither D2 mRNA nor activity increased after an overnight 4 C exposure despite a 10-fold increase in D2 activity in brown adipose tissue in the same mice. The magnitude of the activity, the fiber specificity, and the robust posttranslational response to hypothyroidism argue for a more important role for D2-generated T3 in skeletal muscle physiology than previously assumed.
Type of Medium:
Online Resource
ISSN:
0013-7227
,
1945-7170
DOI:
10.1210/en.2010-0631
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2010
detail.hit.zdb_id:
2011695-0
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