Thyroid hormone drives the expression of mouse carbonic anhydrase Car4 in kidney, lung and brain.

Milica Vujovic, Susi Dudazy-Gralla, Joanna Hård, Peter Solsjö, Amy Warner, Björn Vennström, Jens Mittag

Molecular and cellular endocrinology 2015 Nov 15

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Thyroid hormone is a well-known regulator of brain, lung and kidney development and function. However, the molecular mechanisms by which the hormone exerts its function have remained largely enigmatic, and only a limited set of target genes have been identified in these tissues. Using a mouse model with a mutation in thyroid hormone receptor α1 (TRα1), we here demonstrate that the expression of carbonic anhydrase 4 in lung and brain of the adult animal depends on intact TRα1 signaling. In the kidney, carbonic anhydrase 4 mRNA and protein are not affected by the mutant TRα1, but are acutely repressed by thyroid hormone. However, neither lung function--as measured by respiration rate and oxygen saturation--nor urine pH levels were affected by altered carbonic anhydrase 4 levels, suggesting that other carbonic anhydrases are likely to compensate. Taken together, our findings identify a previously unknown marker of TRα1 action in brain and lung, and provide a novel negatively regulated target gene to assess renal thyroid hormone status. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Citation

Milica Vujovic, Susi Dudazy-Gralla, Joanna Hård, Peter Solsjö, Amy Warner, Björn Vennström, Jens Mittag. Thyroid hormone drives the expression of mouse carbonic anhydrase Car4 in kidney, lung and brain. Molecular and cellular endocrinology. 2015 Nov 15;416:19-26