Regulation of thyroid hormone gatekeepers by TSH in tanycytes.

BACKGROUND: Tanycytes are specialized glial cells within the mediobasal hypothalamus that have multiple functions, including hormone sensing and regulation of hypophysiotropic hormone secretion. There are ongoing discussions about the role of tanycytes in regulating the supply of hypothalamic thyroid hormones (THs) through the expression of TH transporters ( Slc16a2 , Slco1c1 ) and deiodinases ( Dio2 , Dio3 ). In this study, we investigated the potential feedback effect of TSH on the transcription of these gatekeeper genes on tanycytes.

METHODS: We analyzed the changes in the expression of TH gatekeeper genes, in TSH-stimulated primary tanycytes, using qPCR. We also used RNAScope® in brain slices to further reveal the local distribution of the transcripts. In addition, we blocked intracellular pathways and used siRNA to elucidate differences in the regulation of the gatekeeper genes.

RESULTS: TSH elevated mRNA levels of Slco1c1 , Dio2 , and Dio3 in tanycytes, while Slc16a2 was mostly unaffected. Knockdown of the TSH receptor (TSHR) and antagonisation of CREB, clearly abolished the increased expression induced by TSH, indicating PKA-dependent regulation via the TSHR. The TSH-dependent expression of Dio3 and Slco1c1 was additionally regulated by PKC, and in case of Dio3 , also by ERK activity. Importantly, these gene regulations were specifically found in different subpopulations of tanycytes.

CONCLUSIONS: This study demonstrates that, TSH induces transcriptional regulation of TH gatekeeper genes in tanycytes through the Tshr/Gαq/PKC pathway, in parallel to the Tshr/Gαs/PKA/CREB pathway. These differential actions of TSH on tanycytic subpopulations appear to be important for coordinating the supply of TH to the hypothalamus and aid its functions.