Transthyretin (TTR), synthesized by the choroid plexuses (CP) has an important 
role in transporting thyroxine from blood to cerebrospinal fluid (CSF). However, 
the role of TTR on thyroxine transport from CSF to either blood or brain is not 
clear. By using the incubated isolated ovine brain tissues technique, we found 
the CP accumulated most 125I-T4 compared to ventricular ependymal, frontal 
cortex or cerebellum. The accumulation was higher in the young CP than the old. 
There was dose-dependent inhibition by TTR on 125I-T4 accumulation in the brain 
tissues, and kinetics of T4 accumulation in presence of TTR was obtained by 
plotting a double reciprocal of B (bound) versus TTR concentration curve. The KD 
of 125I-T4 binding to TTR was higher in the CP compared to other tissues, 
suggesting that CP competes with TTR for T4 binding to a greater extent than the 
other tissues. Using the isolated perfused CP preparation, TTR significantly 
inhibited 125I-T4 efflux across CP from the CSF to blood side. Bovine serum 
albumin (BSA) was also able to inhibit 125I-T4 accumulation in the incubated 
tissues, but required higher concentrations to reach the level of inhibition 
seen with TTR. In conclusion, this study found a significant role for CSF TTR in 
preventing T4 loss to blood across the CP, and TTR inhibited both CP and 
selected brain tissue uptake in a dose-dependent manner. The physiological 
relevance of TTR may relate to preventing T4 loss from CSF and encouraging 
redistribution of hormone around the brain in CSF.