Regulation of thyroid hormone gatekeepers by TSH in tanycytes

Akila Chandrasekar; Paula Marie Schmidtlein; Vanessa Neve; Manon Rivagorda; Frauke Spiecker; Karine Gauthier; Vincent Prevot; Markus Schwaninger; Helge Müller-Fielitz

doi:10.1089/thy.2023.0375

Regulation of thyroid hormone gatekeepers by TSH in tanycytes

Akila Chandrasekar, Paula Marie Schmidtlein, Vanessa Neve, Manon Rivagorda, Frauke Spiecker, Karine Gauthier, Vincent Prevot, Markus Schwaninger, Helge Müller-Fielitz

Institute of Experimental and Clinical Pharmacology and Toxicology

Abstract

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.

Original language	English
Journal	Thyroid
ISSN	1050-7256
DOIs	https://doi.org/10.1089/thy.2023.0375
Publication status	E-pub ahead of print - 19.12.2023

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

DFG Research Classification Scheme

2.22-17 Endocrinology, Diabetology, Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1089/thy.2023.0375

CRC/Transregio TRR 296 LocoTact: Local control of TH action
Führer-Sakel, D. (Speaker, Coordinator), Mittag, J. (Second Speaker/Coordinator), Kühnen, P. (Second Speaker/Coordinator), Heuer, H. (Principal Investigator (PI)), Schwaninger, M. (Principal Investigator (PI)), Müller-Fielitz, H. (Principal Investigator (PI)), Bechmann, I. (Principal Investigator (PI)), Biebermann, H. (Principal Investigator (PI)), Müller, T. (Principal Investigator (PI)), Pfluger, P. (Principal Investigator (PI)), Krude, H. (Principal Investigator (PI)), Schülke-Gerstenfeld, M. (Principal Investigator (PI)), Cirkel, A. (Principal Investigator (PI)), Münte, T. (Principal Investigator (PI)), Kleinschnitz, C. (Principal Investigator (PI)), Langhauser, F. (Principal Investigator (PI)), Engel, D. R. (Principal Investigator (PI)), Möller, L. (Principal Investigator (PI)), Kaiser, F. (Principal Investigator (PI)), Oster, H. (Principal Investigator (PI)), Kirchner, H. (Principal Investigator (PI)), Spranger, J. (Principal Investigator (PI)), Tacke, F. (Principal Investigator (PI)), Wirth, E. K. (Principal Investigator (PI)), Köhrle, J. (Principal Investigator (PI)), Schomburg, L. (Principal Investigator (PI)), Lange, C. M. (Principal Investigator (PI)), Zwanziger, D. (Principal Investigator (PI)), Mayerl, S. (Principal Investigator (PI)) & Stachelscheid, H. (Principal Investigator (PI))
01.01.20 → …
Project: DFG Projects › DFG Joint Research: Collaborative Research Center/ Transregios

Cite this

@article{0b08cc37e83e43ddbe3688060406eb48,

title = "Regulation of thyroid hormone gatekeepers by TSH in tanycytes",

abstract = "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{\textregistered} 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.",

author = "Akila Chandrasekar and Schmidtlein, {Paula Marie} and Vanessa Neve and Manon Rivagorda and Frauke Spiecker and Karine Gauthier and Vincent Prevot and Markus Schwaninger and Helge M{\"u}ller-Fielitz",

year = "2023",

month = dec,

day = "19",

doi = "10.1089/thy.2023.0375",

language = "English",

journal = "Thyroid",

issn = "1050-7256",

}

TY - JOUR

T1 - Regulation of thyroid hormone gatekeepers by TSH in tanycytes

AU - Chandrasekar, Akila

AU - Schmidtlein, Paula Marie

AU - Neve, Vanessa

AU - Rivagorda, Manon

AU - Spiecker, Frauke

AU - Gauthier, Karine

AU - Prevot, Vincent

AU - Schwaninger, Markus

AU - Müller-Fielitz, Helge

PY - 2023/12/19

Y1 - 2023/12/19

N2 - 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.

AB - 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.

U2 - 10.1089/thy.2023.0375

DO - 10.1089/thy.2023.0375

M3 - Journal articles

C2 - 38115594

SN - 1050-7256

JO - Thyroid

JF - Thyroid

ER -

Regulation of thyroid hormone gatekeepers by TSH in tanycytes

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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Projects

CRC/Transregio TRR 296 LocoTact: Local control of TH action

Cite this