Rodríguez-Rodríguez Adair, Lazcano Iván, Sánchez-Jaramillo Edith, Uribe Rosa María, Jaimes-Hoy Lorraine, Joseph-Bravo Patricia, Charli Jean-Louis
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico.
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla, Mexico.
Front Endocrinol (Lausanne). 2019 Jun 25;10:401. doi: 10.3389/fendo.2019.00401. eCollection 2019.
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 external layer of the median eminence, imbricated intercellular processes may coordinate the flux of TRH into the portal capillaries. In conclusion, β2-tanycytes appear as a critical cellular element for the somatic and post-secretory control of TRH flux into portal vessels, and HPT axis regulation in mammals.
调节能量摄入、分配和消耗的中枢和外周机制决定了能量平衡。甲状腺激素（TH）通过控制基础代谢率和产热来调节能量消耗；它们还调节食物摄入。TH浓度受下丘脑-垂体-甲状腺（HPT）轴以及血液和靶组织中的转运和代谢调节。在哺乳动物中，下丘脑室旁核的促垂体促甲状腺激素释放激素（TRH）神经元整合与能量相关的信息。它们投射到正中隆起（ME）的外侧区，这是一个脑周器官，富含神经元终末曲张体和纽扣、伸长细胞、其他神经胶质细胞和毛细血管。这些毛细血管形成一个门脉系统，将下丘脑底部与垂体前叶连接起来。下丘脑中间基底部的伸长细胞表达一系列参与TH转运、传感和代谢的蛋白质；其中包括2型脱碘酶，它是TRH神经元负反馈所需的3,3',5-三碘-L-甲状腺原氨酸的来源。伸长细胞亚型通过位置和表型来区分。β2-伸长细胞的终足与ME外层的TRH曲张体和终末相互交织，并在靠近ME毛细血管处终止。除了2型脱碘酶外，β2-伸长细胞还表达TRH降解外切酶（TRH-DE）；这种酶可能控制进入门脉血管的TRH量。TRH-DE被TH迅速上调，有助于TH对HPT轴的负反馈。能量平衡的改变也调节ME中TRH-DE的表达和活性，使β2-伸长细胞成为HPT轴活性能量相关调节的枢纽。β2-伸长细胞还表达TRH-R1，它介导TRH对TRH-DE活性以及β2-伸长细胞终足与ME毛细血管相邻基膜接触面积大小的正向作用。这些终足与ME毛细血管的关联以及TRH-DE活性似乎协同控制HPT轴活性。因此，在动作电位到达正中隆起外层导致TRH释放的神经元控制的下游，相互交织的细胞间过程可能协调TRH进入门脉毛细血管的通量。总之，β2-伸长细胞似乎是哺乳动物中TRH通量进入门脉血管的体细胞和分泌后控制以及HPT轴调节的关键细胞元件。
