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

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

doi:10.1038/s41467-017-00604-6

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.

Highlights

The hypothalamic–pituitary–thyroid (HPT) axis maintains circulating thyroid hormone levels in a narrow physiological range
We injected DNA vectors based on recombinant adeno associated virus 1/2 into the lateral ventricle of mice
Thyroid hormones and thyroid-stimulating hormone (TSH) exert a negative feedback at the level of the PVN34 and the pituitary[35] by inhibiting the expression of Trh and Tshb

Summary

Introduction

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. Activation of Gαq/11 pathways increases the size of tanycyte endfeet that shield pituitary vessels and induces the activity of the TRHdegrading ectoenzyme Both mechanisms may limit the TRH release to the pituitary. 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. While α-tanycytes reside dorsally, β-tanycytes occupy the ventral sidewall of the 3rd ventricle and line the floor of the 3rd ventricle in the ME11 Processes of the latter reach to the portal blood vessels in the ME, where their perivascular endfeet are closely associated with axon terminals containing releasing hormones, such as TRH12. Our data demonstrate an important role of tanycytes in the fast regulation of the HPT axis

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