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Effective Cellular Uptake and Efflux of Thyroid Hormone by Human Monocarboxylate Transporter 10

Department of Internal Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Theo J. Visser, Ph.D., Department of Internal Medicine, Erasmus MC, Room Ee502, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail: t.j.visser{at}erasmusmc.nl.

Cellular entry of thyroid hormone is mediated by plasma membrane transporters, among others a T-type (aromatic) amino acid transporter. Monocarboxylate transporter 10 (MCT10) has been reported to transport aromatic amino acids but not iodothyronines. Within the MCT family, MCT10 is most homologous to MCT8, which is a very important iodothyronine transporter but does not transport amino acids. In view of this paradox, we decided to reinvestigate the possible transport of thyroid hormone by human (h) MCT10 in comparison with hMCT8. Transfection of COS1 cells with hMCT10 cDNA resulted in 1) the production of an approximately 55 kDa protein located to the plasma membrane as shown by immunoblotting and confocal microscopy, 2) a strong increase in the affinity labeling of intracellular type I deiodinase by N-bromoacetyl-[¹²⁵I]T₃, 3) a marked stimulation of cellular T₄ and, particularly, T₃ uptake, 4) a significant inhibition of T₃ uptake by phenylalanine, tyrosine, and tryptophan of 12.5%, 22.2%, and 51.4%, respectively, and 5) a marked increase in the intracellular deiodination of T₄ and T₃ by different deiodinases. Cotransfection studies using the cytosolic thyroid hormone-binding protein µ-crystallin (CRYM) indicated that hMCT10 facilitates both cellular uptake and efflux of T₄ and T₃. In the absence of CRYM, hMCT10 and hMCT8 increased T₃ uptake after 5 min incubation up to 4.0- and 1.9-fold, and in the presence of CRYM up to 6.9- and 5.8-fold, respectively. hMCT10 was less active toward T₄ than hMCT8. These findings establish that hMCT10 is at least as active a thyroid hormone transporter as hMCT8, and that both transporters facilitate iodothyronine uptake as well as efflux.

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Ligands:   Thyroid hormone

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