Abstract
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.
Highlights
Thyroid Hormones (TH) are pleiotropic hormones that regulate body physiology throughout vertebrate life
We focus this review on the bidirectional pathways linking medio-basal hypothalamus (MBH) tanycytes with TRH neurons activity and TRH entrance into portal vessels in mammals
We summarize knowledge about tanycytes and their phenotypic variation, demonstrate their critical involvement in TH feedback and adjustment of HPT axis activity according to energy related clues, introduce issues related to tanycyte programing of HPT axis and state some of the existing challenges in non-mammalian vertebrates
Summary
Thyroid Hormones (TH) are pleiotropic hormones that regulate body physiology throughout vertebrate life. While astrocytes supply T3 to brain cells, tanycytes that border the dorso-, ventromedial, and arcuate nuclei, as well as the median eminence, referred here as medio-basal hypothalamus (MBH) tanycytes, contribute to TH feedback on HPT axis, TH control of MBH circuits involved in energy homeostasis [10], as well as regulation of the amount of TRH entering the portal vessels [63, 64].
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