Deiodinase type II is regulated by TRα1 and expressed in pituitary thyrotrophs

Abstract

Thyroid hormones are essential for a variety of developmental and metabolic processes. An important step in the mediation of thyroid hormone action is the conversion of the prohormone T4 to the receptor-active form T3. This is carried out by the deiodinases D1 and D2 through outer ring deiodination (ORD). D2 is known to be expressed in brain, brown adipose tissue, skeletal muscle and pituitary, but its exact localization in the pituitary is unknown so far. It is well established that the expression of D2 mRNA in the pituitary is under strict negative control of thyroid hormones. To analyze the thyroid hormone dependency of D2 mRNA expression, D2 mRNA content of pituitaries from different mouse models lacking thyroid hormone and/or thyroid hormone receptors was investigated using quantitative Realtime-PCR. Compared to wildtype animals and mice deficient in the thyroid hormone receptor α1, D2 mRNA expression was drastically increased in the athyroid Pax8–/– mouse. In contrast, double knockout (Pax8–/–TRα1–/–) mice exhibited no elevated D2 mRNA expression levels despite being completely athyroid like Pax8–/– mutants. Analysis by double in situ hybridization histochemistry revealed that D2 mRNA is not expressed in the thyroid hormone sensitive somatotrophs but in the thyrotrophs. No expression was observed in lactotrophs, corticotrophs and gonadotrophs. These results underline the importance of D2 as a major element of the negative feedback loop controlling TSH mRNA expression by the local generation of T3 in pituitary thyrotrophs. Furthermore, they suggest that D2 gene expression is mainly regulated via the unliganded thyroid hormone receptor α1.