Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis

Helge Müller-Fielitz; Marcus Stahr; Mareike Bernau; Marius Richter; Sebastian Abele; Victor Krajka; Anika Benzin; Jan Wenzel; Kathrin Kalies; Jens Mittag; Heike Heuer; Stefan Offermanns; Markus Schwaninger

doi:10.1038/s41467-017-00604-6

Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis

Helge Müller-Fielitz^*, Marcus Stahr, Mareike Bernau, Marius Richter, Sebastian Abele, Victor Krajka, Anika Benzin, Jan Wenzel, Kathrin Kalies, Jens Mittag, Heike Heuer, Stefan Offermanns, Markus Schwaninger

^*Korrespondierende/r Autor/-in für diese Arbeit

105 Zitate (Scopus)

Abstract

The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating thyroid hormone levels in a narrow physiological range. As axons containing thyrotropin-releasing hormone (TRH) terminate on hypothalamic tanycytes, these specialized glial cells have been suggested to influence the activity of the HPT axis, but their exact role remained enigmatic. Here, we demonstrate that stimulation of the TRH receptor 1 increases intracellular calcium in tanycytes of the median eminence via Gα_q/11 proteins. Activation of Gα_q/11 pathways increases the size of tanycyte endfeet that shield pituitary vessels and induces the activity of the TRH-degrading ectoenzyme. Both mechanisms may limit the TRH release to the pituitary. Indeed, blocking TRH signaling in tanycytes by deleting Gα_q/11 proteins in vivo enhances the response of the HPT axis to the chemogenetic activation of TRH neurons. In conclusion, we identify new TRH- and Gα_q/11-dependent mechanisms in the median eminence by which tanycytes control the activity of the HPT axis.

Originalsprache	Englisch
Aufsatznummer	484
Zeitschrift	Nature Communications
Jahrgang	8
Ausgabenummer	1
ISSN	1751-8628
DOIs	https://doi.org/10.1038/s41467-017-00604-6
Publikationsstatus	Veröffentlicht - 01.12.2017

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Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

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2.22-17 Endokrinologie, Diabetologie, Metabolismus

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10.1038/s41467-017-00604-6

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SFB/Transregio TRR 134: Essverhalten - Homöostase und Belohnungssysteme
Lehnert, H. (Sprecher*in), Brüning, J. C. (Projektleiter*in (PI)), Scholz, H. (Projektleiter*in (PI)), Kloppenburg, P. (Projektleiter*in (PI)), Hausen, A. C. (Projektleiter*in (PI)), Jöhren, O. (Projektleiter*in (PI)), Schulz, C. (Projektleiter*in (PI)), Schwaninger, M. (Projektleiter*in (PI)), Wunderlich, F. T. (Projektleiter*in (PI)), Schmid, S. (Projektleiter*in (PI)), Oster, H. (Projektleiter*in (PI)), Klement, J. (Projektleiter*in (PI)), Ott, V. (Projektleiter*in (PI)), Stephan, K. E. (Projektleiter*in (PI)), Tittgemeyer, M. (Projektleiter*in (PI)), Oltmanns, K. (Projektleiter*in (PI)), Münte, T. (Projektleiter*in (PI)), Tronnier, V. M. (Projektleiter*in (PI)), Schweiger, U. (Projektleiter*in (PI)), Brassen, S. (Projektleiter*in (PI)), Büchel, C. (Projektleiter*in (PI)), Peters, J. (Projektleiter*in (PI)), Schilbach, L. (Projektleiter*in (PI)), Anders, S. (Projektleiter*in (PI)), Martinetz, T. (Projektleiter*in (PI)), Park, S. Q. (Projektleiter*in (PI)), Brabant, E. G. (Projektleiter*in (PI)), Kasten, M. (Projektleiter*in (PI)), Klein, C. (Projektleiter*in (PI)) & Krämer, U. (Projektleiter*in (PI))
01.01.14 → 31.12.18
Projekt: DFG Verbundprojekte › DFG Sonderforschungsbereiche / Transregios (SFB/TR)

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title = "Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis",

abstract = "The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating thyroid hormone levels in a narrow physiological range. As axons containing thyrotropin-releasing hormone (TRH) terminate on hypothalamic tanycytes, these specialized glial cells have been suggested to influence the activity of the HPT axis, but their exact role remained enigmatic. Here, we demonstrate that stimulation of the TRH receptor 1 increases intracellular calcium in tanycytes of the median eminence via Gαq/11 proteins. Activation of Gαq/11 pathways increases the size of tanycyte endfeet that shield pituitary vessels and induces the activity of the TRH-degrading ectoenzyme. Both mechanisms may limit the TRH release to the pituitary. Indeed, blocking TRH signaling in tanycytes by deleting Gαq/11 proteins in vivo enhances the response of the HPT axis to the chemogenetic activation of TRH neurons. In conclusion, we identify new TRH- and Gαq/11-dependent mechanisms in the median eminence by which tanycytes control the activity of the HPT axis.",

author = "Helge M{\"u}ller-Fielitz and Marcus Stahr and Mareike Bernau and Marius Richter and Sebastian Abele and Victor Krajka and Anika Benzin and Jan Wenzel and Kathrin Kalies and Jens Mittag and Heike Heuer and Stefan Offermanns and Markus Schwaninger",

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AU - Müller-Fielitz, Helge

AU - Stahr, Marcus

AU - Bernau, Mareike

AU - Richter, Marius

AU - Abele, Sebastian

AU - Krajka, Victor

AU - Benzin, Anika

AU - Wenzel, Jan

AU - Kalies, Kathrin

AU - Mittag, Jens

AU - Heuer, Heike

AU - Offermanns, Stefan

AU - Schwaninger, Markus

PY - 2017/12/1

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N2 - The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating thyroid hormone levels in a narrow physiological range. As axons containing thyrotropin-releasing hormone (TRH) terminate on hypothalamic tanycytes, these specialized glial cells have been suggested to influence the activity of the HPT axis, but their exact role remained enigmatic. Here, we demonstrate that stimulation of the TRH receptor 1 increases intracellular calcium in tanycytes of the median eminence via Gαq/11 proteins. Activation of Gαq/11 pathways increases the size of tanycyte endfeet that shield pituitary vessels and induces the activity of the TRH-degrading ectoenzyme. Both mechanisms may limit the TRH release to the pituitary. Indeed, blocking TRH signaling in tanycytes by deleting Gαq/11 proteins in vivo enhances the response of the HPT axis to the chemogenetic activation of TRH neurons. In conclusion, we identify new TRH- and Gαq/11-dependent mechanisms in the median eminence by which tanycytes control the activity of the HPT axis.

AB - The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating thyroid hormone levels in a narrow physiological range. As axons containing thyrotropin-releasing hormone (TRH) terminate on hypothalamic tanycytes, these specialized glial cells have been suggested to influence the activity of the HPT axis, but their exact role remained enigmatic. Here, we demonstrate that stimulation of the TRH receptor 1 increases intracellular calcium in tanycytes of the median eminence via Gαq/11 proteins. Activation of Gαq/11 pathways increases the size of tanycyte endfeet that shield pituitary vessels and induces the activity of the TRH-degrading ectoenzyme. Both mechanisms may limit the TRH release to the pituitary. Indeed, blocking TRH signaling in tanycytes by deleting Gαq/11 proteins in vivo enhances the response of the HPT axis to the chemogenetic activation of TRH neurons. In conclusion, we identify new TRH- and Gαq/11-dependent mechanisms in the median eminence by which tanycytes control the activity of the HPT axis.

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VL - 8

JO - Nature Communications

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ER -

Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis

Abstract

UN SDGs

Strategische Forschungsbereiche und Zentren

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Projekte

SFB/Transregio TRR 134: Essverhalten - Homöostase und Belohnungssysteme

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