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

^*Corresponding author for this work

97 Citations (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.

Original language	English
Article number	484
Journal	Nature Communications
Volume	8
Issue number	1
ISSN	1751-8628
DOIs	https://doi.org/10.1038/s41467-017-00604-6
Publication status	Published - 01.12.2017

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

SDG 3 Good Health and Well-being

Research Areas and Centers

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

DFG Research Classification Scheme

2.22-17 Endocrinology, Diabetology, Metabolism

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10.1038/s41467-017-00604-6

Cite this

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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.",

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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

Y1 - 2017/12/1

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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M3 - Journal articles

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SN - 1751-8628

VL - 8

JO - Nature Communications

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ER -

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

Abstract

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CRC/Transregio TRR 134: Ingestive Behaviour: Homeostasis and Reward

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

Abstract

UN SDGs

Research Areas and Centers

DFG Research Classification Scheme

Access to Document

Other files and links

Fingerprint

Projects

CRC/Transregio TRR 134: Ingestive Behaviour: Homeostasis and Reward

Cite this