Expression of beta2-thyroid hormone receptor in euthyroid and hypothyroid rat pituitary gland: an in situ...

Recently, we have shown an extended distribution pattern of the TR-beta2 isoform in specific sites of rat brain which may be indicative that the localization of this receptor also confers functional specificity. The beta2 thyroid hormone receptor (TR-beta2) is by far the most abundant isoform in the pituitary, although transcripts of TR-alpha and TR-beta1 genes have been reported in developmental and adult rat pituitary gland. Using both in situ hybridization histochemistry (ISH) and immunocytochemistry, we mapped the expression of beta2 thyroid hormone receptor mRNA and protein in euthyroid and hypothyroid adult rat pituitary, particularly in relation to the thyrotrope population. TR-beta2 mRNA localization by ISH showed an anteromedial spatial distribution pattern in euthyroid rat anterior pituitary gland. This localization coincided with the immunostaining pattern for thyrotropes. TR-beta2-immunoreactive cells showed strongly positive signals in the nuclei. Hypothyroidism, induced by propylthiouracil (PTU), abolished the specific localization of TR-beta2 mRNA and upregulated the transcription of TR-beta2 mRNA in vivo and in vitro. Image analysis revealed that the optical density signals within hypothyroid rat pituitary were significantly stronger (2.6-fold) compared with euthyroid counterparts. This correlated strongly with an increased number and staining of TR-beta2 protein positive cells, demonstrating both nuclear and cytoplasmic staining. In response to thyroid hormone deficiency, there was also a marked percentage increase in the thyrotrope population from 10 to 20% of anterior pituitary cells to approximately 80%. In conclusion, these results demonstrate the specific localization of TR-beta2 to the anterior pituitary, especially to the thyrotrope population, and its regulation by thyroid hormone. Hypothyroidism leads to an upregulation of TR-beta2 mRNA and protein in the anterior pituitary, explained not only by an absolute increase in the percentage of thyrotropes but increased expression of TR-beta2 mRNA and protein per cell. These data allude to the TR-beta2 isoform playing a critical role in thyroid hormone-dependent TSH gene expression, although contributions from the other TR isoforms may still remain important.