Abstract

The actions and the metabolism of thyroid hormone are intracellular events that require the transport of iodothyronines across the plasma membrane. It is increasingly clear that this process does not occur by simple diffusion, but is facilitated by transport proteins. Only recently have iodothyronine transporters been identified at the molecular level, of which organic anion transporting polypeptide 1C1 and monocarboxylate transporter 8 (MCT8) deserve special mention, because of their high activity and specificity for iodothyronines. Organic anion transporting polypeptide 1C1 is almost exclusively expressed in brain capillaries, and may be crucial for the transport of the prohormone T₄ across the blood–brain barrier. MCT8 is also expressed in the brain—in particular, in neurons—but also in other tissues. MCT8 seems to be especially important for the uptake of active hormone T₃ into neurons, which is essential for optimal brain development. T₃ is produced from T₄ by type 2 deiodinase in neighboring astrocytes. Neurons express type 3 deiodinase, the enzyme that terminates T₃ activity. The SLC16A2 (formerly MCT8) gene is located on chromosome Xq13.2 and has recently been associated with a syndrome combining severe, X-linked, psychomotor retardation and high serum T₃ levels. In over 20 families, where affected males have developed this syndrome, several mutations in MCT8 have been identified. The disease mechanism is thought to involve a defect in the neuronal entry of T₃ and, therefore, in the action and metabolism of T₃ in these cells. This defect results in impaired neurological development and a decrease in T₃ clearance.

Author affiliations

1. ECH Friesema is a Post-Doctoral Fellow, J Jansen is a PhD Fellow, and TJ Visser is a Professor of Endocrinology at the Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands;
2. H Heuer is a Group Leader, and M Trajkovic is a PhD Fellow at the Leibniz Institute for Age Research—Fritz Lipmann Institute, Jena, Germany;
3. K Bauer is a Professor of Endocrinology at the Max Planck Institute for Experimental Endocrinology, Hannover, Germany.

Correspondence to: Theo J Visser¹ Department of Internal Medicine, Room Ee502, Erasmus Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
Email: t.j.visser@erasmusmc.nl

Received 14 October 2005 | Accepted 23 May 2006