Efflux of thyroxine and its brain distribution from the cerebrospinal fluid

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University of Bristol (2001) J Physiol 536P, S168

Communications: Efflux of thyroxine and its brain distribution from the cerebrospinal fluid

N.A. Kassem, R. Deane* and M.B. Segal

Centre for Neuroscience Research, King's College London, St Thomas' Hospital, London SE1 7EH and * School of Chemical and Life Sciences, University of Greenwich, London SE18 6PF, UK

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The thyroid hormones thyroxine (T4) and tri-iodothyronine (T3), are synthesised outside the brain, and have important effects on the growth, development and metabolism of the central nervous system (Moore et al. 1973; Pickard et al. 1987). However, the mechanism of transport of these hormones across the blood-brain and blood-CSF barriers is unclear. The choroid plexus (CP) secretes the thyroxine transporting protein transthyretin (TTR) into the cerebrospinal fluid (CSF), but the role of TTR in the transport of T4 from the blood via CP into the CSF and brain is still controversial. By using the bilateral ventriculo-cisternal perfusion (VC) technique (Davson & Segal, 1970), in anaesthetised rabbits (Domitor and pentobarbitone given I.V. at a dose of 0.5 mg and 10 mg kg-1, respectively), we have investigated the movement of 125I-T4 (10 µCi (50 ml)-1 out of a mock CSF perfusate (ACSF) and its distribution into the brain. The experiment was terminated by an overdose of anaesthetic. We have demonstrated a large loss of T4 from the CSF of about 40 %, which was not inhibited by excess of unlabelled T4 or by sodium perchlorate (5 mM in ACSF), the latter indicating that the efflux was not due to the uptake of free iodide. The uptake of 125I-T4 into brain regions around ventricles was: hippocampus 21 ± 8.3 % (n = 3), frontal cortex 19 ± 3.4 % (n = 3) and parietal cortex 13 ± 0.3 % (n = 3). Since the CP showed a higher accumulation of the T4 during 4 h perfusion (712 ± 211.7 %), compared with 2 h (168 ± 47.02 %) (P < 0.01, Student’s unpaired t test), it appears that the large loss of T4 from the CSF might be due to an efflux mechanism by this tissue. Studies are in progress to determine the route and possible mechanism of this efflux process. Values given are means ± S.E.M.

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

    Davson, H. & Segal, M.B. (1970). J. Physiol. 209, 131-153. abstract

    Moore, T.J., Armand, P., Lione, A.P. & Regan, D.M. (1973). Am. J. Physiol. 225, 925-929.

    Pickard, R., Sinha, A.K., Gullo, D., Patel, N., Hubank, M. & Ekins, R.P. (1987). Endocrinology 121, 2018-2026.

Where applicable, experiments conform with Society ethical requirements.

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