Investigating how tanycytes integrate central thyroid hormone signals

The hypothalamus-pituitary-thyroid (HPT) axis is one of several hormone regulatory systems connecting the hypothalamus to its peripheral target organs and plays a fundamental role in maintaining the normal serum levels of circulating thyroid hormones (THs) and thus the euthyroid state. At the interface of the HPT - the third ventricle - reside the tanycytes, specialised ependymoglial cells. Their anatomical location allows tanycytes to act as gatekeepers of the HPT and regulate both the output of thyroid releasing hormone (TRH) and the entry of peripheral THs to the brain. Recently, it was shown that primary cilia (PC) protrude from the tanycytes’ apical surface into the cerebrospinal fluid. Primary cilia are organelles highly enriched in G-coupled protein receptors and ion channels making them excellent mediators for regulating endocrine pathways. Consequently, in this project we investigate whether tanycytic cilia, named tanycilia, play a role in integrating TH signals and thus regulating the HPT axis. For this purpose, we used immunohistochemistry to characterize tanycilia morphology in a mouse model of TH transporters knockout (Mct8/Oatpc1 DKO). In vitro, we characterized the tanycilia morphology in primary cultures of tanycytes stimulated with THs, in normal condition and after impairment of tanycilia function. At the functional level, we found that the increase in intracellular calcium concentration in response to the TRH analogue Taltirelin was weakened in tanycytes displaying impaired cilia. Investigating the precise mechanisms by which tanycytes regulate the HPT axis is key to elucidate the central effects of defective HPT signalling in pathologies like central hypothyroidism.