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Title: Type 1 iodothyronine deiodinase is a sensitive marker of peripheral thyroid status in the mouse
Authors: Zavacki, AM ×
Ying, H
Christoffolete, MA
Aerts, Goele
So, E
Harney, JW
Cheng, SY
Larsen, PR
Bianco, AC #
Issue Date: Mar-2005
Publisher: Endocrine soc
Series Title: Endocrinology vol:146 issue:3 pages:1568-1575
Abstract: Mice with one thyroid hormone receptor (TR) alpha-1 allele encoding a dominant negative mutant receptor (TRalpha1(PV/+)) have persistently elevated serum T-3 levels (1.9-fold above normal). They also have markedly increased hepatic type 1 iodothyronine deiodinase (D1) mRNA and enzyme activity (4- to 5-fold), whereas other hepatic T-3-responsive genes, such as Spot14 and mitochondrial alpha-glycerol phosphate dehydrogenase (alpha-GPD), are only 0.7-fold and 1.7-fold that of wild-type littermates (TRalpha1(+/+)). To determine the cause of the disproportionate elevation of D1, TRalpha1(+/+) and TRalpha1(PV/+) mice were rendered hypothyroid and then treated with T-3. Hypothyroidism decreased hepatic D1, Spot14, and alpha-GPD mRNA to similar levels in TRalpha1(+/+) and TRalpha1(PV/+) 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 alpha-GPD mRNAs. Interestingly, the hypothyroidism-induced increase in cerebrocortical type 2 iodothyronine deiodinase activity was 3 times greater in the TRalpha1(PV/+) mice, and these mice had no T-3-dependent induction of type 3 iodothyronine deiodinase. Thus, the marked responsiveness of hepatic D1 to T-3 relative to other genes, such as Spot14 and alpha-GPD, explains the relatively large effect of the modest increase in serum T-3 in the TRalpha1(PV/+) mice, and TRalpha plays a key role in T-3-dependent positive and negative regulation of the deiodinases in the cerebral cortex.
URI: 
ISSN: 0013-7227
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Animal Physiology and Neurobiology Section - miscellaneous
× corresponding author
# (joint) last author

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