Open AccessMice With Hepatocyte-Specific Deficiency of Type 3 Deiodinase Have Intact Liver Regeneration and Accelerated Recovery From Nonthyroidal Illness After Toxin-Induced Hepatonecrosis
Author(s) -
Luciana Audi Castroneves,
Rebecca H. Jugo,
Michelle Maynard,
Jennifer Lee,
Ari J. Wassner,
David M. Dorfman,
Roderick T. Bronson,
Chinweike Ukomadu,
Agoston T. Agoston,
Lai Ding,
Cristina Luongo,
Cuicui Guo,
HuaiDong Song,
Valeriy Demchev,
Nicholas Y. Lee,
Henry A. Feldman,
Kristen R. Vella,
Roy W A Peake,
Christina E. Hartigan,
Mark D. Kellogg,
Anal Desai,
Domenico Salvatore,
Monica Dentice,
Stephen A. Huang
Publication year - 2014
Publication title -
endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.674
H-Index - 257
eISSN - 1945-7170
pISSN - 0013-7227
DOI - 10.1210/en.2013-2028
Subject(s) - endocrinology , medicine , hepatocyte , triiodothyronine , deiodinase , iodothyronine deiodinase , regeneration (biology) , biology , hormone , thyroid , necrosis , liver injury , toxin , microbiology and biotechnology , biochemistry , in vitro
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.
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