Type 1 iodothyronine deiodinase is a sensitive marker of peripheral thyroid status in the mouse

Ann Marie Zavacki, Hao Ying, Marcelo A. Christoffolete, Goele Aerts, Edward So, John W. Harney, Sheue Yann Cheng, P. Reed Larsen, Antonio C. Bianco

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97 Scopus citations

Abstract

Mice with one thyroid hormone receptor (TR) aα-1 allele encoding a dominant negative mutant receptor (TRα1PV/+) have persistently elevated serum T3 levels (1.9-fold above normal). They also have markedly increased hepatic type 1 iodotbyronine deiodinase (D1) mBNA and enzyme activity (4- to 5-fold), whereas other hepatic T3-respoasive genes, such as Spot14 and mitochondrial α-glycerol phosphate dehydrogenase (α-GPD), are only 0.7-fold and 1.7-fold that of wild-type littermates (TRα1+/+). To determine the cause of the disproportionate elevation of D1, TRα1+/+ and TRα1PV/+ mice were rendered hypothyroid and then treated with T3. Hypothyroidism decreased hepatic D1, Spot14, and α-GPD mRNA to similar levels in TRα1+/+ and TRα1PV/+ mice, whereas T 3 administration caused an approximately 175-fold elevation of D1 mRNA but only a 3- to 6-fold increases in Spot14 and α-GPD mRNAs. Interestingly, the hypothyroidism-induced increase in cerebrocortical type 2 iodothyronine deiodinase activity was times greater in the TRα1 PV/+ mice, and these mice had no T3-dependent induction of type 3 iodothyronine deiodinase. Thus, the marked responsiveness of hepatic D1 to T3 relative to other genes, such as Spot14 and α-GPD, explains the relatively large effect of the modest increase in serum T 3 in the TRα1PV/+ mice, and TRα plays a key role in T3-dependent positive and negative regulation of the deiodinases in the cerebral cortex.

Original languageEnglish (US)
Pages (from-to)1568-1575
Number of pages8
JournalEndocrinology
Volume146
Issue number3
DOIs
StatePublished - Mar 1 2005

ASJC Scopus subject areas

  • Endocrinology

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    Zavacki, A. M., Ying, H., Christoffolete, M. A., Aerts, G., So, E., Harney, J. W., Cheng, S. Y., Larsen, P. R., & Bianco, A. C. (2005). Type 1 iodothyronine deiodinase is a sensitive marker of peripheral thyroid status in the mouse. Endocrinology, 146(3), 1568-1575. https://doi.org/10.1210/en.2004-1392