The thyroid hormones thyroxine (T4) and triiodothyronine (T3) are synthesized outside the brain, and are essential for normal growth and development of the central nervous system (Moore et al. 1973; Pickard et al. 1987). T4 can enter the brain via two pathways, directly through the bloodÐbrain barrier (BBB) and across the choroid plexus (CP) into the cerebrospinal fluid (CSF) and then diffusing into the extracellular space around the neurones. TTR is a thyroxine-binding protein, synthesized by the CP and secreted into the CSF, and is proposed to play a role in the transport of T4 in the brain. However, the role of TTR in the distribution of T4 into different areas of the brain is still controversial. By using the bilateral ventriculo-cisternal perfusion (VC) technique (Davson & Segal, 1970) in anaesthetized rabbits (Domitor and pentobarbitone given I.V. at a dose of 0.5 mg and 10 mg kg^-1, respectively), we have investigated the efflux of ¹²⁵I-T4 (10 mCi (50 ml)^-1) out of the ACSF perfusate, and the uptake into the surrounding tissues (animals were killed humanely at the end of the experiment). We have shown a large loss of T4 from the CSF, about 45 %. At a TTR concentration of 2.5 mg ml^-1 ACSF, as TTR/T4 complex, the loss was significantly inhibited by 25 % (P = 0.004, Student’s unpaired t test, n = 3). ¹²⁵I-T4 uptake into the brain was significantly increased in the presence of TTR as TTR/T4 complex, i.e. caudate nucleus uptake increased from 8.23 ± 2.87 to 45.11 ± 8.03 ml (100 g)^-1 (P = 0.006, n = 3); values are means ± S.E.M. We conclude that TTR increases the uptake of T4 into the surrounding brain tissues and decreases the loss from the CSF. These results suggest that TTR plays an important role in the removal and distribution of T4 in the central nervous system. Studies are in progress to determine the route and possible mechanism of these processes.

This work was supported by The Al-Tajir World of Islam Trust.

All procedures accord with current UK legislation.