title: Mice with hepatocyte-specific deficiency of type 3 deiodinase have intact liver regeneration and accelerated recovery from nonthyroidal illness after toxin-induced hepatonecrosis.
abstract: 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.
authors.affiliation: 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.), Clinical Research Center (H.A.F), and Department of Laboratory Medicine (R.W.P., C.H., M.D.K), Boston Children's Hospital; Thyroid Section of the Division of Endocrinology, Diabetes, and Hypertension (S.A.H.), Department of Pathology (D.D., A.T.A.), and Division of Gastroenterology (C.U., V.D., A.D.), Brigham and Women's Hospital; Harvard Neurodiscovery Center (L.D.); Dana Farber Cancer Institute (R.T. B., S.A.H.); Division of Endocrinology (K.R.V.), Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115; and Department of Molecular and Clinical Endocrinology and Oncology (C.L., D.S., M.D.), University of Naples Federico II, 80131 Naples, Italy.
authors.forename: Luciana A
authors.initials: LA
authors.lastname: Castroneves
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Jugo
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Maynard
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Lee
authors.forename: Ari J
authors.initials: AJ
authors.lastname: Wassner
authors.forename: David
authors.initials: D
authors.lastname: Dorfman
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Chinweike
authors.initials: C
authors.lastname: Ukomadu
authors.forename: Agoston T
authors.initials: AT
authors.lastname: Agoston
authors.forename: Lai
authors.initials: L
authors.lastname: Ding
authors.forename: Cristina
authors.initials: C
authors.lastname: Luongo
authors.forename: Cuicui
authors.initials: C
authors.lastname: Guo
authors.forename: Huaidong
authors.initials: H
authors.lastname: Song
authors.forename: Valeriy
authors.initials: V
authors.lastname: Demchev
authors.forename: Nicholas Y
authors.initials: NY
authors.lastname: Lee
authors.forename: Henry A
authors.initials: HA
authors.lastname: Feldman
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Vella
authors.forename: Roy W
authors.initials: RW
authors.lastname: Peake
authors.forename: Christina
authors.initials: C
authors.lastname: Hartigan
authors.forename: Mark D
authors.initials: MD
authors.lastname: Kellogg
authors.forename: Anal
authors.initials: A
authors.lastname: Desai
authors.forename: Domenico
authors.initials: D
authors.lastname: Salvatore
authors.forename: Monica
authors.initials: M
authors.lastname: Dentice
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Huang
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000503:physiopathology / Q000534:rehabilitation*; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000172:deficiency / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis / Q000139:chemically induced / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D020127:Recovery of Function / Q000235:genetics; D014118:Toxins, Biological
chemical_list: D014118:Toxins, Biological; D002251:Carbon Tetrachloride; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase