Title :

Regulation of thyroid hormone gatekeepers by TSH in tanycytes.

Author(s) :

Chandrasekar, A. [Auteur]
Universität zu Lübeck = University of Lübeck [Lübeck]
Schmidtlein, P. M. [Auteur]
Universität zu Lübeck = University of Lübeck [Lübeck]
Neve, V. [Auteur]
Universität zu Lübeck = University of Lübeck [Lübeck]
Rivagorda, M. [Auteur]
Universität zu Lübeck = University of Lübeck [Lübeck]
Spiecker, F. [Auteur]
Universität zu Lübeck = University of Lübeck [Lübeck]
Gauthier, K. [Auteur]
Institut de Génomique Fonctionnelle de Lyon [IGFL]
Prevot, Vincent [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Schwaninger, M. [Auteur]
Müller-Fielitz, H. [Auteur]
Universität zu Lübeck = University of Lübeck [Lübeck]

Journal title :

Thyroid

Abbreviated title :

Thyroid

Volume number :

34

Pages :

261-273

Publication date :

2023-12-20

ISSN :

1557-9077

English keyword(s) :

PKC
PKA
thyroid hormone transporter
deiodinase
TSH
tanycytes

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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 thyrotropin (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 quantitative polymerase chain reaction (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 small-interfering RNA (siRNA) to elucidate differences in the regulation of the gatekeeper genes. Results: TSH elevated messenger RNA (mRNA) levels of Slco1c1, Dio2, and Dio3 in tanycytes, while Slc16a2 was mostly unaffected. Blockade and knockdown of the TSH receptor (TSHR) and antagonization of cAMP response element-binding protein (CREB) clearly abolished the increased expression induced by TSH, indicating PKA-dependent regulation through the TSHR. The TSH-dependent expression of Dio3 and Slco1c1 was also regulated by protein kinase C (PKC), and in case of Dio3, also by extracellular signal-regulated kinase (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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Submission date :

2024-02-17T22:08:25Z
2024-05-24T07:35:38Z