TY - JOUR
T1 - Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis
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.
UR - http://www.scopus.com/inward/record.url?scp=85029046698&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-00604-6
DO - 10.1038/s41467-017-00604-6
M3 - Journal articles
C2 - 28883467
AN - SCOPUS:85029046698
SN - 1751-8628
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 484
ER -
