Hypothalamic tanycytes are polarized ependymoglial cells lining the base of the third ventricle and extending processes toward the median eminence (ME), where they contact fenestrated capillaries, forming a key blood–brain communication interface. We investigated whether glucocorticoids (GCs) induce structural remodeling of tanycytes and how this affects local blood–brain exchange. Wild-type mice received dexamethasone (Dex, 1 mg/kg i.p.) or vehicle for five days. Dex increased the accessibility of plasma-derived molecules to the ME, assessed by Evans blue extravasation. This effect was accompanied by a reduction in the tanycyte–vascular interface and by glucocorticoid receptor (GR) nuclear translocation in tanycytes in vivo. In primary rat tanycyte cultures, Dex induced terminal retraction and shortening of cellular processes, as revealed by live-cell imaging recordings and morphometric analysis of fixed cells. These effects were reversible and prevented by the GR antagonist RU-486. Furthermore, Dex promoted early transcriptional activation and increased vimentin expression in cultured tanycytes, as determined by c-Fos and vimentin immunofluorescence quantification, respectively. Together, these findings identify tanycytes as dynamic regulators of blood-to-brain communication in the hypothalamus and demonstrate that GCs remodel their vascular interface through a GR-dependent mechanism, increasing the accessibility of circulating molecules to the ME.
