{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T18:32:17Z","timestamp":1759602737848},"reference-count":32,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Type 3 deiodinase (D3), the physiologic inactivator of thyroid hormones, is induced during tissue injury and regeneration. This has led to the hypotheses that D3 impacts injury tolerance by reducing local T3 signaling and contributes to the fall in serum triiodothyronine (T3) observed in up to 75% of sick patients (termed the low T3 syndrome). Here we show that a novel mutant mouse with hepatocyte-specific D3 deficiency has normal local responses to toxin-induced hepatonecrosis, including normal degrees of tissue necrosis and intact regeneration, but accelerated systemic recovery from illness-induced hypothyroxinemia and hypotriiodothyroninemia, demonstrating that peripheral D3 expression is a key modulator of the low T3 syndrome.<\/jats:p>","DOI":"10.1210\/en.2013-2028","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T17:30:38Z","timestamp":1404840638000},"page":"4061-4068","source":"Crossref","is-referenced-by-count":7,"title":["Mice With Hepatocyte-Specific Deficiency of Type 3 Deiodinase Have Intact Liver Regeneration and Accelerated Recovery From Nonthyroidal Illness After Toxin-Induced Hepatonecrosis"],"prefix":"10.1210","volume":"155","author":[{"given":"Luciana A.","family":"Castroneves","sequence":"first","affiliation":[{"name":"Thyroid Program of the Division of Endocrinology (L.A.C., R.H.J., M.A.M., J.S.L., A.J.W., C.C.G., H.D.S., N.Y.L., S.A.H.), Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca H.","family":"Jugo","sequence":"first","affiliation":[{"name":"Thyroid Program of the Division of Endocrinology (L.A.C., R.H.J., M.A.M., J.S.L., A.J.W., C.C.G., H.D.S., N.Y.L., S.A.H.), Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle A.","family":"Maynard","sequence":"first","affiliation":[{"name":"Thyroid Program of the Division of Endocrinology (L.A.C., R.H.J., M.A.M., J.S.L., A.J.W., C.C.G., H.D.S., N.Y.L., S.A.H.), Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer S.","family":"Lee","sequence":"first","affiliation":[{"name":"Thyroid Program of the Division of Endocrinology (L.A.C., R.H.J., M.A.M., J.S.L., A.J.W., C.C.G., H.D.S., N.Y.L., S.A.H.), Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ari J.","family":"Wassner","sequence":"first","affiliation":[{"name":"Thyroid Program of the Division of Endocrinology (L.A.C., R.H.J., M.A.M., J.S.L., A.J.W., C.C.G., H.D.S., N.Y.L., S.A.H.), Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Dorfman","sequence":"first","affiliation":[{"name":"Department of Pathology (D.D., A.T.A.), Brigham and Women's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roderick T.","family":"Bronson","sequence":"first","affiliation":[{"name":"Dana Farber Cancer Institute (R.T. B., S.A.H.), Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chinweike","family":"Ukomadu","sequence":"first","affiliation":[{"name":"Division of Gastroenterology (C.U., V.D., A.D.), Brigham and Women's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agoston T.","family":"Agoston","sequence":"first","affiliation":[{"name":"Department of Pathology (D.D., A.T.A.), Brigham and Women's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lai","family":"Ding","sequence":"first","affiliation":[{"name":"Harvard Neurodiscovery Center (L.D.), Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Luongo","sequence":"first","affiliation":[{"name":"Department of Molecular and Clinical Endocrinology and Oncology (C.L., D.S., M.D.), University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cuicui","family":"Guo","sequence":"first","affiliation":[{"name":"Thyroid Program of the Division of Endocrinology (L.A.C., R.H.J., M.A.M., J.S.L., A.J.W., C.C.G., H.D.S., N.Y.L., S.A.H.), Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaidong","family":"Song","sequence":"first","affiliation":[{"name":"Thyroid Program of the Division of Endocrinology (L.A.C., R.H.J., M.A.M., J.S.L., A.J.W., C.C.G., H.D.S., N.Y.L., S.A.H.), Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeriy","family":"Demchev","sequence":"first","affiliation":[{"name":"Division of Gastroenterology (C.U., V.D., A.D.), Brigham and Women's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas Y.","family":"Lee","sequence":"first","affiliation":[{"name":"Thyroid Program of the Division of Endocrinology (L.A.C., R.H.J., M.A.M., J.S.L., A.J.W., C.C.G., H.D.S., N.Y.L., S.A.H.), Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry A.","family":"Feldman","sequence":"first","affiliation":[{"name":"Clinical Research Center (H.A.F), Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen R.","family":"Vella","sequence":"first","affiliation":[{"name":"Division of Endocrinology (K.R.V.), Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy W.","family":"Peake","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine (R.W.P., C.H., M.D.K), Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Hartigan","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine (R.W.P., C.H., M.D.K), Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark D.","family":"Kellogg","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine (R.W.P., C.H., M.D.K), Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anal","family":"Desai","sequence":"first","affiliation":[{"name":"Division of Gastroenterology (C.U., V.D., A.D.), Brigham and Women's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Salvatore","sequence":"first","affiliation":[{"name":"Department of Molecular and Clinical Endocrinology and Oncology (C.L., D.S., M.D.), University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Dentice","sequence":"first","affiliation":[{"name":"Department of Molecular and Clinical Endocrinology and Oncology (C.L., D.S., M.D.), University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen A.","family":"Huang","sequence":"first","affiliation":[{"name":"Thyroid Program of the Division of Endocrinology (L.A.C., R.H.J., M.A.M., J.S.L., A.J.W., C.C.G., H.D.S., N.Y.L., S.A.H.), Boston Children's Hospital"},{"name":"Thyroid Section of the Division of Endocrinology, Diabetes, and Hypertension (S.A.H.), Brigham and Women's Hospital"},{"name":"Dana Farber Cancer Institute (R.T. B., S.A.H.), Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071612374271600_B1","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1210\/jc.2002-021291","article-title":"Type 3 iodothyronine deiodinase is highly expressed in the human uteroplacental unit and in fetal epithelium","volume":"88","author":"Huang","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612374271600_B2","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1172\/JCI26240","article-title":"Type 3 deiodinase is critical for the maturation and function of the thyroid axis","volume":"116","author":"Hernandez","year":"2006","journal-title":"J Clin Invest"},{"key":"2020071612374271600_B3","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":"2020071612374271600_B4","first-page":"975","article-title":"Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats","volume":"118","author":"Simonides","year":"2008","journal-title":"J Clin Invest"},{"key":"2020071612374271600_B5","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1210\/en.2010-0431","article-title":"Left-ventricular remodeling after myocardial infarction is associated with a cardiomyocyte-specific hypothyroid condition","volume":"152","author":"Pol","year":"2011","journal-title":"Endocrinology"},{"key":"2020071612374271600_B6","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":"2020071612374271600_B7","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1089\/thy.2008.0090","article-title":"Type 3 deiodinase is highly expressed in infiltrating neutrophilic granulocytes in response to acute bacterial infection","volume":"18","author":"Boelen","year":"2008","journal-title":"Thyroid"},{"key":"2020071612374271600_B8","doi-asserted-by":"crossref","first-page":"5190","DOI":"10.1210\/endo.142.12.8532","article-title":"Induction of type 3 iodothyronine deiodinase by nerve injury in the rat peripheral nervous system","volume":"142","author":"Li","year":"2001","journal-title":"Endocrinology"},{"key":"2020071612374271600_B9","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1056\/NEJM200007203430305","article-title":"Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas","volume":"343","author":"Huang","year":"2000","journal-title":"N Engl J Med"},{"key":"2020071612374271600_B10","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1056\/NEJMoa1308893","article-title":"Thyroid hormone inactivation in gastrointestinal stromal tumors","volume":"370","author":"Maynard","year":"2014","journal-title":"N Engl J Med"},{"key":"2020071612374271600_B11","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1210\/en.2008-0344","article-title":"Large induction of type III deiodinase expression after partial hepatectomy in the regenerating mouse and rat liver","volume":"150","author":"Kester","year":"2009","journal-title":"Endocrinology"},{"key":"2020071612374271600_B12","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/ncpendmet0727","article-title":"Reawakened interest in type III iodothyronine deiodinase in critical illness and injury","volume":"4","author":"Huang","year":"2008","journal-title":"Nat Clin Pract Endocrinol Metab"},{"key":"2020071612374271600_B13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1210\/en.2008-1460","article-title":"Deiodination and cellular proliferation: parallels between development, differentiation, tumorigenesis, and now regeneration","volume":"150","author":"Huang","year":"2009","journal-title":"Endocrinology"},{"key":"2020071612374271600_B14","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cmet.2009.11.003","article-title":"Irs1 serine 307 promotes insulin sensitivity in mice","volume":"11","author":"Copps","year":"2010","journal-title":"Cell metabolism"},{"key":"2020071612374271600_B15","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/nprot.2008.80","article-title":"A reproducible and well-tolerated method for 2\/3 partial hepatectomy in mice","volume":"3","author":"Mitchell","year":"2008","journal-title":"Nat Protoc"},{"key":"2020071612374271600_B16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/9780470942390.mo130087","article-title":"Inducing and characterizing liver regeneration in mice: Reliable models, essential \u201creadouts\u201d and critical perspectives","volume":"3","author":"Mastellos","year":"2013","journal-title":"Curr Protoc Mouse Biol"},{"key":"2020071612374271600_B17","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":"2020071612374271600_B18","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":"2020071612374271600_B19","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1210\/endo-104-1-58","article-title":"Subcellular alterations causing reduced hepatic thyroxine-5\u2032-monodeiodinase activity in fasted fats","volume":"104","author":"Kaplan","year":"1979","journal-title":"Endocrinology"},{"key":"2020071612374271600_B20","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1128\/MCB.00129-14","article-title":"Thyroid hormone signaling in vivo requires a balance between coactivators and corepressors","volume":"34","author":"Vella","year":"2014","journal-title":"Mol Cell Biol"},{"key":"2020071612374271600_B21","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/353273a0","article-title":"Recognition of UGA as a selenocysteine codon in type I deiodinase requires sequences in the 3\u2032 untranslated region","volume":"353","author":"Berry","year":"1991","journal-title":"Nature"},{"key":"2020071612374271600_B22","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1074\/jbc.274.1.305","article-title":"Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase","volume":"274","author":"Postic","year":"1999","journal-title":"J Biol Chem"},{"key":"2020071612374271600_B23","doi-asserted-by":"crossref","first-page":"5680","DOI":"10.1210\/en.2007-0652","article-title":"Type 3 deiodinase deficiency results in functional abnormalities at multiple levels of the thyroid axis","volume":"148","author":"Hernandez","year":"2007","journal-title":"Endocrinology"},{"key":"2020071612374271600_B24","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1073\/pnas.0610774104","article-title":"Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1","volume":"104","author":"Sadler","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612374271600_B25","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1210\/en.2007-0029","article-title":"Gene expression from the imprinted Dio3 locus is associated with cell proliferation of cultured brown adipocytes","volume":"148","author":"Hernandez","year":"2007","journal-title":"Endocrinology"},{"key":"2020071612374271600_B26","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/ncb1272","article-title":"The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate","volume":"7","author":"Dentice","year":"2005","journal-title":"Nat Cell Biol"},{"key":"2020071612374271600_B27","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1053\/j.gastro.2012.06.042","article-title":"\u03b2-Catenin Regulates Deiodinase Levels and Thyroid Hormone Signaling in Colon Cancer Cells","volume":"143","author":"Dentice","year":"2012","journal-title":"Gastroenterology"},{"key":"2020071612374271600_B28","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1016\/j.bbagen.2012.05.007","article-title":"The deiodinases and the control of intracellular thyroid hormone signaling during cellular differentiation","volume":"1830","author":"Dentice","year":"2013","journal-title":"Biochimic Biophys Acta"},{"key":"2020071612374271600_B29","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1172\/JCI66025","article-title":"Liver sinusoidal endothelial cells and liver regeneration","volume":"123","author":"DeLeve","year":"2013","journal-title":"J Clin Invest"},{"key":"2020071612374271600_B30","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.surg.2012.06.021","article-title":"Angiogenesis is crucial for liver regeneration after partial hepatectomy","volume":"153","author":"Uda","year":"2013","journal-title":"Surgery"},{"key":"2020071612374271600_B31","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1053\/j.gastro.2012.08.008","article-title":"Hepatic vascular endothelial growth factor regulates recruitment of rat liver sinusoidal endothelial cell progenitor cells","volume":"143","author":"Wang","year":"2012","journal-title":"Gastroenterology"},{"key":"2020071612374271600_B32","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1210\/en.2008-1133","article-title":"Impaired bacterial clearance in type 3 deiodinase-deficient mice infected with Streptococcus pneumoniae","volume":"150","author":"Boelen","year":"2009","journal-title":"Endocrinology"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/155\/10\/4061\/10827464\/endo4061.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/155\/10\/4061\/10827464\/endo4061.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T21:07:30Z","timestamp":1594933650000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/155\/10\/4061\/2423649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,1]]},"references-count":32,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2014,10,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2013-2028","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,1]]}}}