Type 2 iodothyronine deiodinase levels are higher in slow-twitch than fast-twitch mouse skeletal muscle and are increased in hypothyroidism.
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 T(4) 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 < 0.001). These levels are greater than those previously reported. Hypothyroidism caused a 40% (P < 0.01) and 300% (P < 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 T(3) in skeletal muscle physiology than previously assumed.
Marsili
Alessandro
A
Thyroid Section, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.
Ramadan
Waile
W
Harney
John W
JW
Mulcahey
Michelle
M
Castroneves
Luciana Audi
LA
Goemann
Iuri Martin
IM
Wajner
Simone Magagnin
SM
Huang
Stephen A
SA
Zavacki
Ann Marie
AM
Maia
Ana Luiza
AL
Dentice
Monica
M
Salvatore
Domenico
D
Silva
J Enrique
JE
Larsen
P Reed
PR
D000818:Animals; D000831:Animals, Newborn; D013956:Antithyroid Agents / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
D013956:Antithyroid Agents; D007453:Iodide Peroxidase; D008713:Methimazole; D012333:RNA, Messenger; D000097564:Iodothyronine Deiodinase Type II