REVIEW published: 25 June 2019 doi: 10.3389/fendo.2019.00401 Frontiers in Endocrinology | www.frontiersin.org 1 June 2019 | Volume 10 | Article 401 Edited by: María A. García, Universidad de Concepción, Chile Reviewed by: Vincent Prevot, Institut National de la Santé et de la Recherche Médicale (INSERM), France Marie-Stéphanie Clerget-Froidevaux, Muséum National D’Histoire Naturelle (France), France Seiji Miyata, Kyoto Institute of Technology, Japan *Correspondence: Jean-Louis Charli charli@ibt.unam.mx Specialty section: This article was submitted to Neuroendocrine Science, a section of the journal Frontiers in Endocrinology Received: 28 February 2019 Accepted: 06 June 2019 Published: 25 June 2019 Citation: Rodríguez-Rodríguez A, Lazcano I, Sánchez-Jaramillo E, Uribe RM, Jaimes-Hoy L, Joseph-Bravo P and Charli J-L (2019) Tanycytes and the Control of Thyrotropin-Releasing Hormone Flux Into Portal Capillaries. Front. Endocrinol. 10:401. doi: 10.3389/fendo.2019.00401 Tanycytes and the Control of Thyrotropin-Releasing Hormone Flux Into Portal Capillaries Adair Rodríguez-Rodríguez 1 , Iván Lazcano 2 , Edith Sánchez-Jaramillo 3 , Rosa María Uribe 1 , Lorraine Jaimes-Hoy 1 , Patricia Joseph-Bravo 1 and Jean-Louis Charli 1 * 1 Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico, 2 Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla, Mexico, 3 Laboratorio de Neuroendocrinología Molecular, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City, Mexico Central and peripheral mechanisms that modulate energy intake, partition and expenditure determine energy homeostasis. Thyroid hormones (TH) regulate energy expenditure through the control of basal metabolic rate and thermogenesis; they also modulate food intake. TH concentrations are regulated by the hypothalamus-pituitary-thyroid (HPT) axis, and by transport and metabolism in blood and target tissues. In mammals, hypophysiotropic thyrotropin-releasing hormone (TRH) neurons of the paraventricular nucleus of the hypothalamus integrate energy-related information. They project to the external zone of the median eminence (ME), a brain circumventricular organ rich in neuron terminal varicosities and buttons, tanycytes, other glial cells and capillaries. These capillary vessels form a portal system that links the base of the hypothalamus with the anterior pituitary. Tanycytes of the medio-basal hypothalamus express a repertoire of proteins involved in transport, sensing, and metabolism of TH; among them is type 2 deiodinase, a source of 3,3 ′ ,5-triiodo-L-thyronine necessary for negative feedback on TRH neurons. Tanycytes subtypes are distinguished by position and phenotype. The end-feet of β2-tanycytes intermingle with TRH varicosities and terminals in the external layer of the ME and terminate close to the ME capillaries. Besides type 2 deiodinase, β2-tanycytes express the TRH-degrading ectoenzyme (TRH-DE); this enzyme likely controls the amount of TRH entering portal vessels. TRH-DE is rapidly upregulated by TH, contributing to TH negative feedback on HPT axis. Alterations in energy balance also regulate the expression and activity of TRH-DE in the ME, making β2-tanycytes a hub for energy-related regulation of HPT axis activity. β2-tanycytes also express TRH-R1, which mediates positive effects of TRH on TRH-DE activity and the size of β2-tanycyte end-feet contacts with the basal lamina adjacent to ME capillaries. These end-feet associations with ME capillaries, and TRH-DE activity, appear to coordinately control HPT axis activity. Thus, down-stream of neuronal control of TRH release by action potentials arrival in the