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Pathophysiological Importance of Thyroid Hormone Transporters

Neuroendocrinology Group, Leibniz Institute for Age Research/Fritz Lipmann Institute, D-07745 Jena, Germany; and Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Theo J. Visser, Department of Internal Medicine, Section of Endocrinology, Erasmus Medical College, Room Ee 502, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail: t.j.visser{at}erasmusmc.nl.

Abstract

Thyroid hormone metabolism and action are largely intracellular events that require transport of iodothyronines across the plasma membrane. It has been assumed for a long time that this occurs by passive diffusion, but it has become increasingly clear that cellular uptake and efflux of thyroid hormone is mediated by transporter proteins. Recently, several active and specific thyroid hormone transporters have been identified, including monocarboxylate transporter 8 (MCT8), MCT10, and organic anion transporting polypeptide 1C1 (OATP1C1). The latter is expressed predominantly in brain capillaries and transports preferentially T₄, whereas MCT8 and MCT10 are expressed in multiple tissues and are capable of transporting different iodothyronines. The pathophysiological importance of thyroid hormone transporters has been established by the demonstration of MCT8 mutations in patients with severe psychomotor retardation and elevated serum T₃ levels. MCT8 appears to play an important role in the transport of thyroid hormone in the brain, which is essential for the crucial action of the hormone during brain development. It is expected that more specific thyroid hormone transporters will be discovered in the near future, which will lead to a better understanding of the tissue-specific regulation of thyroid hormone bioavailability.