{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:06:51Z","timestamp":1790762811810,"version":"4.1.0"},"reference-count":41,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:p>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 \u00b1 0.06 vs. 0.076 \u00b1 0.01 fmol\/min \u00b7 mg microsomal protein, respectively, P &amp;lt; 0.001). These levels are greater than those previously reported. Hypothyroidism caused a 40% (P &amp;lt; 0.01) and 300% (P &amp;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.<\/jats:p>","DOI":"10.1210\/en.2010-0631","type":"journal-article","created":{"date-parts":[[2010,9,30]],"date-time":"2010-09-30T04:19:36Z","timestamp":1285820376000},"page":"5952-5960","source":"Crossref","is-referenced-by-count":60,"title":["Type 2 Iodothyronine Deiodinase Levels Are Higher in Slow-Twitch than Fast-Twitch Mouse Skeletal Muscle and Are Increased in Hypothyroidism"],"prefix":"10.1210","volume":"151","author":[{"given":"Alessandro","family":"Marsili","sequence":"first","affiliation":[{"name":"Thyroid Section (A.M., J.W.H., A.M.Z., P.R.L.), Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waile","family":"Ramadan","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism (W.R., J.E.S.), Baystate Medical Center, Tufts University School of Medicine, Springfield, Massachusetts 01199"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Harney","sequence":"first","affiliation":[{"name":"Thyroid Section (A.M., J.W.H., A.M.Z., P.R.L.), Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Mulcahey","sequence":"first","affiliation":[{"name":"Thyroid Program (M.M., L.A.C., S.A.H.), Department of Endocrinology, Children\u2019s Hospital, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana Audi","family":"Castroneves","sequence":"first","affiliation":[{"name":"Thyroid Program (M.M., L.A.C., S.A.H.), Department of Endocrinology, Children\u2019s Hospital, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iuri Martin","family":"Goemann","sequence":"first","affiliation":[{"name":"Thyroid Section (I.M.G., S.M.W., A.L.M.), Endocrine Division, Hospital de Cli\u0301nicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre RS-90035-003, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone Magagnin","family":"Wajner","sequence":"first","affiliation":[{"name":"Thyroid Section (I.M.G., S.M.W., A.L.M.), Endocrine Division, Hospital de Cli\u0301nicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre RS-90035-003, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Huang","sequence":"first","affiliation":[{"name":"Thyroid Program (M.M., L.A.C., S.A.H.), Department of Endocrinology, Children\u2019s Hospital, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann Marie","family":"Zavacki","sequence":"first","affiliation":[{"name":"Thyroid Section (A.M., J.W.H., A.M.Z., P.R.L.), Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Luiza","family":"Maia","sequence":"first","affiliation":[{"name":"Thyroid Section (I.M.G., S.M.W., A.L.M.), Endocrine Division, Hospital de Cli\u0301nicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre RS-90035-003, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Dentice","sequence":"first","affiliation":[{"name":"Department of Molecular and Clinical Endocrinology and Oncology (M.D., D.S.), University of Naples \u201cFederico II,\u201d 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Salvatore","sequence":"first","affiliation":[{"name":"Department of Molecular and Clinical Endocrinology and Oncology (M.D., D.S.), University of Naples \u201cFederico II,\u201d 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Enrique","family":"Silva","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism (W.R., J.E.S.), Baystate Medical Center, Tufts University School of Medicine, Springfield, Massachusetts 01199"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Reed","family":"Larsen","sequence":"first","affiliation":[{"name":"Thyroid Section (A.M., J.W.H., A.M.Z., P.R.L.), Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2010,9,29]]},"reference":[{"key":"2020071612482608400_R1","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/35007527","article-title":"Towards a molecular understanding of adaptive thermogenesis.","volume":"404","author":"Lowell","year":"2000","journal-title":"Nature"},{"key":"2020071612482608400_R2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1089\/thy.2007.0256","article-title":"Thyroid hormone as a determinant of metabolic and contractile phenotype of skeletal muscle.","volume":"18","author":"Simonides","year":"2008","journal-title":"Thyroid"},{"key":"2020071612482608400_R3","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1172\/JCI114857","article-title":"Skeletal muscle metabolism is a major determinant of resting energy expenditure.","volume":"86","author":"Zurlo","year":"1990","journal-title":"J Clin Invest"},{"key":"2020071612482608400_R4","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1152\/physrev.00009.2005","article-title":"Thermogenic mechanisms and their hormonal regulation.","volume":"86","author":"Silva","year":"2006","journal-title":"Physiol Rev"},{"key":"2020071612482608400_R5","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1101\/gr.207702","article-title":"In vivo regulation of human skeletal muscle gene expression by thyroid hormone.","volume":"12","author":"Cle\u0301ment","year":"2002","journal-title":"Genome Res"},{"key":"2020071612482608400_R6","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1210\/jc.2009-0782","article-title":"Physiological thyroid hormone levels regulate numerous skeletal muscle transcripts.","volume":"94","author":"Visser","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612482608400_R7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1210\/edrv.23.1.0455","article-title":"Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases.","volume":"23","author":"Bianco","year":"2002","journal-title":"Endocr Rev"},{"key":"2020071612482608400_R8","doi-asserted-by":"crossref","first-page":"4626","DOI":"10.1210\/endo.139.11.6323","article-title":"Direct measurement of the contributions of type I and type II 5\u2032-deiodinases to whole body steady state 3,5,3\u2032-triiodothyronine production from thyroxine in the rat.","volume":"139","author":"Nguyen","year":"1998","journal-title":"Endocrinology"},{"key":"2020071612482608400_R9","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.1172\/JCI25083","article-title":"Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans.","volume":"115","author":"Maia","year":"2005","journal-title":"J Clin Invest"},{"key":"2020071612482608400_R10","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1210\/endo.137.8.8754756","article-title":"Molecular biological and biochemical characterization of the human type 2 selenodeiodinase.","volume":"137","author":"Salvatore","year":"1996","journal-title":"Endocrinology"},{"key":"2020071612482608400_R11","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1172\/JCI118806","article-title":"Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues.","volume":"98","author":"Croteau","year":"1996","journal-title":"J Clin Invest"},{"key":"2020071612482608400_R12","doi-asserted-by":"crossref","first-page":"6471","DOI":"10.1210\/en.2008-0718","article-title":"Mice lacking the thyroid hormone receptor-\u03b1 gene spend more energy in thermogenesis, burn more fat, and are less sensitive to high-fat diet-induced obesity.","volume":"149","author":"Pelletier","year":"2008","journal-title":"Endocrinology"},{"key":"2020071612482608400_R13","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1210\/en.2008-0938","article-title":"Type 2 deiodinase expression is induced by peroxisomal proliferator-activated receptor-gamma agonists in skeletal myocytes.","volume":"150","author":"Grozovsky","year":"2009","journal-title":"Endocrinology"},{"key":"2020071612482608400_R14","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1210\/jc.2008-2520","article-title":"Type 2 iodothyronine deiodinase in skeletal muscle: effects of hypothyroidism and fasting.","volume":"94","author":"Heemstra","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612482608400_R15","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1210\/jc.2007-0510","article-title":"The type II iodothyronine deiodinase is up-regulated in skeletal muscle during prolonged critical illness.","volume":"92","author":"Mebis","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612482608400_R16","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1111\/j.1365-2265.2007.03102.x","article-title":"Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock.","volume":"68","author":"Rodriguez-Perez","year":"2008","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071612482608400_R17","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1677\/JOE-09-0118","article-title":"Skeletal muscle deiodinase type 2 regulation during illness in mice.","volume":"203","author":"Kwakkel","year":"2009","journal-title":"J Endocrinol"},{"key":"2020071612482608400_R18","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1210\/endo.141.3.7355","article-title":"Substrate-induced down-regulation of human type 2 deiodinase (hD2) is mediated through proteasomal degradation and requires interaction with the enzyme\u2019s active center.","volume":"141","author":"Steinsapir","year":"2000","journal-title":"Endocrinology"},{"key":"2020071612482608400_R19","doi-asserted-by":"crossref","first-page":"577","DOI":"10.2337\/diabetes.53.3.577","article-title":"Mice with targeted disruption of the Dio2 gene have cold-induced overexpression of the uncoupling protein 1 gene but fail to increase brown adipose tissue lipogenesis and adaptive thermogenesis.","volume":"53","author":"Christoffolete","year":"2004","journal-title":"Diabetes"},{"key":"2020071612482608400_R20","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1210\/mend.15.12.0740","article-title":"Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4.","volume":"15","author":"Schneider","year":"2001","journal-title":"Mol Endocrinol"},{"key":"2020071612482608400_R21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1210\/endo.142.1.7907","article-title":"Type 2 iodothyronin deiodinase transgene expression in the mouse heart causes cardiac-specific thyrotoxicosis.","volume":"142","author":"Pachucki","year":"2001","journal-title":"Endocrinology"},{"key":"2020071612482608400_R22","first-page":"2868","article-title":"Ontogeny of iodothyronine deiodinases in human liver.","volume":"83","author":"Richard","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612482608400_R23","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1210\/en.2004-1392","article-title":"Type 1 iodothyronine deiodinase is a sensitive marker of peripheral thyroid status in the mouse.","volume":"146","author":"Zavacki","year":"2005","journal-title":"Endocrinology"},{"key":"2020071612482608400_R24","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1089\/thy.2009.0318","article-title":"Impaired metabolic effects of a thyroid hormone receptor \u03b2-selective agonist in a mouse model of diet-induced obesity.","volume":"20","author":"Castillo","year":"2010","journal-title":"Thyroid"},{"key":"2020071612482608400_R25","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1172\/JCI41977","article-title":"Paracrine signaling by glial cell-derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells.","volume":"120","author":"Freitas","year":"2010","journal-title":"J Clin Invest"},{"key":"2020071612482608400_R26","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1210\/jc.2002-022013","article-title":"Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients.","volume":"88","author":"Peeters","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612482608400_R27","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1172\/JCI118299","article-title":"Type 3 lodothyronine deiodinase: cloning, in vitro expression, and the functional analysis of the placental selenoenzyme.","volume":"96","author":"Salvatore","year":"1995","journal-title":"J Clin Invest"},{"key":"2020071612482608400_R28","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cbpc.2004.09.021","article-title":"Seven skeletal muscles rich in slow muscle fibers may function to sustain neutral position in the rodent hindlimb.","volume":"140","author":"Hitomi","year":"2005","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"2020071612482608400_R29","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1177\/21.1.51","article-title":"Hindlimb muscle fiber populations of five mammals.","volume":"21","author":"Ariano","year":"1973","journal-title":"J Histochem Cytochem"},{"key":"2020071612482608400_R30","doi-asserted-by":"crossref","first-page":"5231","DOI":"10.1210\/endo.138.12.5602","article-title":"Thyroid hormones inhibit type 2 iodothyronine deiodinase in the rat cerebral cortex by both pre- and posttranslational mechanisms.","volume":"138","author":"Burmeister","year":"1997","journal-title":"Endocrinology"},{"key":"2020071612482608400_R31","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/BF02534498","article-title":"Iodothyronines: oxidative deiodination by hemoglobin and inhibition of lipid peroxidation.","volume":"19","author":"Tseng","year":"1984","journal-title":"Lipids"},{"key":"2020071612482608400_R32","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1210\/jc.2004-1977","article-title":"The type 2 deiodinase A\/G (Thr92Ala) polymorphism is associated with decreased enzyme velocity and increased insulin resistance in patients with type 2 diabetes mellitus.","volume":"90","author":"Canani","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612482608400_R33","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1210\/er.2008-0019","article-title":"Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling.","volume":"29","author":"Gereben","year":"2008","journal-title":"Endocr Rev"},{"key":"2020071612482608400_R34","doi-asserted-by":"crossref","first-page":"5339","DOI":"10.1128\/MCB.01498-08","article-title":"The E3 ubiquitin ligase TEB4 mediates degradation of type 2 iodothyronine deiodinase.","volume":"29","author":"Zavacki","year":"2009","journal-title":"Mol Cell Biol"},{"key":"2020071612482608400_R35","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1210\/en.2009-1049","article-title":"Thyroid hormone receptor \u03b1 modulates lipopolysaccharide-induced changes in peripheral thyroid hormone metabolism.","volume":"151","author":"Kwakkel","year":"2010","journal-title":"Endocrinology"},{"key":"2020071612482608400_R36","first-page":"177","article-title":"Mouse skeletal muscle microsomes have type-2 iodothyronine deiodinase (D2) mRNA and activity. Possible role in hypermetabolism of TR deficient mice","author":"Ramadan","year":"2009"},{"key":"2020071612482608400_R37","doi-asserted-by":"crossref","first-page":"4559","DOI":"10.1210\/jc.2005-0535","article-title":"Serum 3,3\u2032,5\u2032-triiodothyronine (rT3) and 3,5,3\u2032-triiodothyronine\/rT3 are prognostic markers in critically ill patients and are associated with postmortem tissue deiodinase activities.","volume":"90","author":"Peeters","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612482608400_R38","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1177\/002215540004800506","article-title":"Fiber type composition of the vastus lateralis muscle of young men and women.","volume":"48","author":"Staron","year":"2000","journal-title":"J Histochem Cytochem"},{"key":"2020071612482608400_R39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1530\/acta.0.0900081","article-title":"A methodological study in measuring T3 and T4 concentration in red and white skeletal muscle and plasma of euthyroid rats.","volume":"90","author":"Janssen","year":"1979","journal-title":"Acta Endocrinol (Copenh)"},{"key":"2020071612482608400_R40","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1172\/JCI110699","article-title":"Comparison of iodothyronine 5\u2032-deiodinase and other thyroid-hormone-dependent enzyme activities in the cerebral cortex of hypothyroid neonatal rat. Evidence for adaptation to hypothyroidism.","volume":"70","author":"Silva","year":"1982","journal-title":"J Clin Invest"},{"key":"2020071612482608400_R41","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1172\/JCI109598","article-title":"Physiological and pharmacological influences on thyroxine to 3,5,3\u2032-triiodothyronine conversion and nuclear 3,5,3\u2032-triiodothyronine binding in rat anterior pituitary.","volume":"64","author":"Cheron","year":"1979","journal-title":"J Clin Invest"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/151\/12\/5952\/9011201\/endo5952.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/151\/12\/5952\/9011201\/endo5952.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T21:57:30Z","timestamp":1594936650000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/151\/12\/5952\/2456382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,29]]},"references-count":41,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2010,12,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2010-0631","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,29]]}}}