Transport of thyroxine across the blood-brain barrier is directed primarily from brain to blood in the mouse

The role of the blood-brain barrier (BBB) in the transport of thyroxine was examined in mice. Radioiodinated (hot thyroxine (hT4) administered icv had a half-time disappearance from the brain of 30 min. This increased to 60 min (p < 0.001) when administered with 211 pmole/mouse of unlabeled (cold) thyroxine (cT4). The Km for this inhibition of hT4 transport out of the brain by cT4 was 9.66 pmole/brain. Unlabeled 3,3',5 triiodothyronine (cT3) was unable to inhibit transport of hT4 out of the brain, although both cT3 (p < 0.05) and cT4 (p < 0.05) did inhibit transport of radioiodinated 3,3',5 triiodothyronine (hT3) to a small degree. Entry of hT4 into the brain after peripheral administration was negligible and was not affected by either cT4 nor cT3. By contrast, the entry of hT3 into the brain after peripheral administration was inhibited by cT3 (p < 0.001) and was increased by cT4 (p < 0.01). The levels of the unlabeled thyroid hormones administered centrally in these studies did not affect bulk flow, as assessed by labeled red blood cells (/sup 99m/Tc-RBC), or the carrier mediated transport of iodide out of the brain. Likewise, the vascular space of the brain and body, as assessed by /sup 99m/Tc-RBC, was unchanged by the levels of peripherally administered unlabeled thyroid hormones. Therefore, the results of these studies are not due to generalized effects of thyroid hormones on BBB transport. The results indicate that in the mouse the major carrier-mediated system for thyroxine in the BBB transports thyroxine out of the brain, while the major system for triiodothyronine transports hormone into the brain. 14 references, 3 figures, 2 tables