title: Type 2 iodothyronine deiodinase levels are higher in slow-twitch than fast-twitch mouse skeletal muscle and are increased in hypothyroidism.
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 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.
authors.affiliation: Thyroid Section, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marsili
authors.forename: Waile
authors.initials: W
authors.lastname: Ramadan
authors.forename: John W
authors.initials: JW
authors.lastname: Harney
authors.forename: Michelle
authors.initials: M
authors.lastname: Mulcahey
authors.forename: Luciana Audi
authors.initials: LA
authors.lastname: Castroneves
authors.forename: Iuri Martin
authors.initials: IM
authors.lastname: Goemann
authors.forename: Simone Magagnin
authors.initials: SM
authors.lastname: Wajner
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Huang
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Zavacki
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Maia
authors.forename: Monica
authors.initials: M
authors.lastname: Dentice
authors.forename: Domenico
authors.initials: D
authors.lastname: Salvatore
authors.forename: J Enrique
authors.initials: JE
authors.lastname: Silva
authors.forename: P Reed
authors.initials: PR
authors.lastname: Larsen
mesh_terms: 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
chemical_list: D013956:Antithyroid Agents; D007453:Iodide Peroxidase; D008713:Methimazole; D012333:RNA, Messenger; D000097564:Iodothyronine Deiodinase Type II