Type 1 iodothyronine deiodinase is a sensitive marker of peripheral thyroid status in the mouse
AM Zavacki, H Ying, MA Christoffolete, G Aerts… - …, 2005 - academic.oup.com
Endocrinology, 2005•academic.oup.com
Mice with one thyroid hormone receptor (TR) α-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 iodothyronine deiodinase (D1)
mRNA and enzyme activity (4-to 5-fold), whereas other hepatic T3-responsive 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 …
mutant receptor (TRα1PV/+) have persistently elevated serum T3 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 T3-responsive 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 …
Mice with one thyroid hormone receptor (TR) α-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 iodothyronine deiodinase (D1) mRNA and enzyme activity (4- to 5-fold), whereas other hepatic T3-responsive 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 T3 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 3 times greater in the TRα1PV/+ 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 T3 in the TRα1PV/+ mice, and TRα plays a key role in T3-dependent positive and negative regulation of the deiodinases in the cerebral cortex.
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