Inactivation of Thyroid Hormone Transporters Mct8/Oatp1c1 in Mouse Brain Endothelial Cells Causes Region-Specific Alterations in Central Thyroid Hormone Signaling

Deficiency of Mct8 and Oatp1c1 in endothelial cells results in reduced murine brain TH content and TH action, thereby underscoring the major function of BBB endothelial Mct8/Oatp1c1 in facilitating TH uptake into the CNS. Yet, the degree of central TH deficiency and neural impairments in Endo del mice are not as profound as in DKO mice. Particularly, unaltered hippocampal T3 signaling suggests a sufficient T3 supply of this brain area, possibly via the cerebrospinal fluid (CSF). These findings infer that apart from the BBB, additional Mct8/Oatp1c1-facilitated TH transmembrane passages (for instance, TH transport across the blood-CSF barrier) are required for proper mouse brain development and function.