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

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.

Tanycytes: A rich morphological history to underpin future molecular and physiological investigations

“…95 In the third ventricle of the rabbit, a great number of axons with bulb-like endings have been described by Leonhardt and Backhus-Roth. 95 In the third ventricle of the rabbit, a great number of axons with bulb-like endings have been described by Leonhardt and Backhus-Roth.…”

“…tanycytes and increases the size of tanycyte end-feet resulting in a reduction in TRH release into the portal blood. 95 In the third ventricle of the rabbit, a great number of axons with bulb-like endings have been described by Leonhardt and Backhus-Roth. 94 These terminals contain small clear vesicles, dense cored vesicles and mitochondria.…”

Ablation of tanycytes of the arcuate nucleus and median eminence increases visceral adiposity and decreases insulin sensitivity in male mice

“…Significant increases in serum TSH and neurotensin levels were observed in tanycyte-ablated mice following short-term treatment ( . Because tanycytes produce thyroid hormone converting enzyme [29], and have been linked to regulation of TRH release from hypothalamic neurosecretory cells [9,19,30], we further investigated whether short-term tanycyte-ablation compromised the response of the hypothalamic-pituitary-thyroid axis to an acute cold challenge. While serum TSH levels were consistently elevated following 2 hour cold exposure, no significant difference was observed between control and tanycyte-ablated mice ( Fig.…”

“…Their location at the interface between the hypothalamus and circulatory system allows tanycytes to regulate a broad range of processes relevant to hypothalamic physiology. These include control of the blood-hypothalamus barrier [3,4], energy and nutrient sensing [5][6][7], and regulation of neurohormone release [8,9]. Tanycytes also express many markers of neural progenitor cells, and have been reported to show limited neurogenic potential [10][11][12].Recently, there has been growing interest in the potential role of tanycytes in regulating energy metabolism [5,13,14].…”

“…Tanycytes also express many markers of neural progenitor cells, and have been reported to show limited neurogenic potential [10][11][12].Recently, there has been growing interest in the potential role of tanycytes in regulating energy metabolism [5,13,14]. Tanycytes have been reported to directly sense glucose and amino acid levels in CSF and blood [15][16][17], to actively transport leptin into the hypothalamus [18], and to regulate production and release of thyroid releasing hormone (TRH) [9,19]. However, these studies have not directly investigated whether tanycytes are indeed necessary for regulating these processes.…”