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Nat Commun. 2017 Sep 7;8(1):484. doi: 10.1038/s41467-017-00604-6.

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

Author information

1
Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany. helge.mueller-fielitz@pharma.uni-luebeck.de.
2
Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
3
Institute of Anatomy, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
4
Department of Internal Medicine, Molecular Endocrinology, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
5
Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany.
6
Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Ludwigstraße 43, 61231, Bad Nauheim, Germany.
7
Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany. markus.schwaninger@pharma.uni-luebeck.de.

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.The hypothalamic-pituitary-thyroid (HPT) axis regulates a wide range of physiological processes. Here the authors show that hypothalamic tanycytes play a role in the homeostatic regulation of the HPT axis; activation of TRH signaling in tanycytes elevates their intracellular Ca2+ via Gαq/11 pathway, ultimately resulting in reduced TRH release into the pituitary vessels.

PMID:
28883467
PMCID:
PMC5589884
DOI:
10.1038/s41467-017-00604-6
[Indexed for MEDLINE]
Free PMC Article

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