This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Friesema, E. C. H. Articles by Kester, M. H. A. Search for Related Content PubMed PubMed Citation Articles by Friesema, E. C. H. Articles by Kester, M. H. A.

Thyroid Hormone Transport by the Human Monocarboxylate Transporter 8 and Its Rate-Limiting Role in Intracellular Metabolism

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. We have identified rat monocarboxylate transporter 8 (MCT8) as an active and specific thyroid hormone transporter. The MCT8 gene is located on the X-chromosome. The physiological relevance of MCT8 has been demonstrated by the identification of hemizygous mutations in this gene in males with severe psychomotor retardation and elevated serum T₃ levels. We have characterized human (h) MCT8 by analysis of iodothyronine uptake and metabolism in cell lines transiently transfected with hMCT8 cDNA alone or together with cDNA coding for iodothyronine deiodinase D1, D2, or D3. MCT8 mRNA was detected by RT-PCR in a number of human cell lines as well as in COS1 cells but was low to undetectable in other cell lines, including JEG3 cells. MCT8 protein was not detected in nontransfected cell lines tested by immunoblotting using a polyclonal C-terminal hMCT8 antibody but was detectable in transfected cells at the expected size (61 kDa). Transfection of COS1 and JEG3 cells with hMCT8 cDNA resulted in 2- to 3-fold increases in uptake of T₃ and T₄ but little or no increase in rT₃ or 3,3'-diiodothyronine (3,3'-T₂) uptake. MCT8 expression produced large increases in T₄ metabolism by cotransfected D2 or D3, T₃ metabolism by D3, rT₃ metabolism by D1 or D2, and 3,3'-T₂ metabolism by D3. Affinity labeling of hMCT8 protein was observed after incubation of intact transfected cells with N-bromoacetyl-[¹²⁵I]T₃. hMCT8 also facilitated affinity labeling of cotransfected D1 by bromoacetyl-T₃. Our findings indicate that hMCT8 mediates plasma membrane transport of iodothyronines, thus increasing their intracellular availability.

NURSA Molecule Pages Link:

Ligands:   Thyroid hormone

This article has been cited by other articles:

				M. Trajkovic-Arsic, T. J. Visser, V. M. Darras, E. C. H. Friesema, B. Schlott, J. Mittag, K. Bauer, and H. Heuer Consequences of Monocarboxylate Transporter 8 Deficiency for Renal Transport and Metabolism of Thyroid Hormones in Mice Endocrinology, February 1, 2010; 151(2): 802 - 809. [Abstract] [Full Text] [PDF]

				L. C. Heather, M. A. Cole, H. J. Atherton, W. A. Coumans, R. D. Evans, D. J. Tyler, J. F. C. Glatz, J. J. F. P. Luiken, and K. Clarke Adenosine Monophosphate-Activated Protein Kinase Activation, Substrate Transporter Translocation, and Metabolism in the Contracting Hyperthyroid Rat Heart Endocrinology, January 1, 2010; 151(1): 422 - 431. [Abstract] [Full Text] [PDF]

				W. E. Visser, N. J. Philp, T. B. van Dijk, W. Klootwijk, E. C. H. Friesema, J. Jansen, P. W. Beesley, A. G. Ianculescu, and T. J. Visser Evidence for a Homodimeric Structure of Human Monocarboxylate Transporter 8 Endocrinology, November 1, 2009; 150(11): 5163 - 5170. [Abstract] [Full Text] [PDF]

				C. Di Cosmo, X.-H. Liao, A. M. Dumitrescu, R. E. Weiss, and S. Refetoff A Thyroid Hormone Analog with Reduced Dependence on the Monocarboxylate Transporter 8 for Tissue Transport Endocrinology, September 1, 2009; 150(9): 4450 - 4458. [Abstract] [Full Text] [PDF]

				L. Mebis, D. Paletta, Y. Debaveye, B. Ellger, L. Langouche, A. D'Hoore, V. M Darras, T. J Visser, and G. Van den Berghe Expression of thyroid hormone transporters during critical illness Eur. J. Endocrinol., August 1, 2009; 161(2): 243 - 250. [Abstract] [Full Text] [PDF]

				M. Vujovic, K. Nordstrom, K. Gauthier, F. Flamant, T. J. Visser, B. Vennstrom, and J. Mittag Interference of a Mutant Thyroid Hormone Receptor {alpha}1 with Hepatic Glucose Metabolism Endocrinology, June 1, 2009; 150(6): 2940 - 2947. [Abstract] [Full Text] [PDF]

				S. R. James, J. A. Franklyn, B. J. Reaves, V. E. Smith, S. Y. Chan, T. G. Barrett, M. D. Kilby, and C. J. McCabe Monocarboxylate Transporter 8 in Neuronal Cell Growth Endocrinology, April 1, 2009; 150(4): 1961 - 1969. [Abstract] [Full Text] [PDF]

				W. E. Visser, E. C. H. Friesema, and T. J. Visser Transport of Thyroxine and 3,3',5-Triiodothyronine in Human Umbilical Vein Endothelial Cells Endocrinology, March 1, 2009; 150(3): 1552 - 1557. [Abstract] [Full Text] [PDF]

				H. Heuer and T. J. Visser Pathophysiological Importance of Thyroid Hormone Transporters Endocrinology, March 1, 2009; 150(3): 1078 - 1083. [Abstract] [Full Text] [PDF]

				B. Gereben, A. M. Zavacki, S. Ribich, B. W. Kim, S. A. Huang, W. S. Simonides, A. Zeold, and A. C. Bianco Cellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling Endocr. Rev., December 1, 2008; 29(7): 898 - 938. [Abstract] [Full Text] [PDF]

				W. M. van der Deure, P. S. Hansen, R. P. Peeters, K. O. Kyvik, E. C. H. Friesema, L. Hegedus, and T. J. Visser Thyroid Hormone Transport and Metabolism by Organic Anion Transporter 1C1 and Consequences of Genetic Variation Endocrinology, October 1, 2008; 149(10): 5307 - 5314. [Abstract] [Full Text] [PDF]

				W. M. van der Deure, E. C. H. Friesema, F. J. de Jong, Y. B. de Rijke, F. H. de Jong, A. G. Uitterlinden, M. M. B. Breteler, R. P. Peeters, and T. J. Visser Organic Anion Transporter 1B1: An Important Factor in Hepatic Thyroid Hormone and Estrogen Transport and Metabolism Endocrinology, September 1, 2008; 149(9): 4695 - 4701. [Abstract] [Full Text] [PDF]

				E. C. H. Friesema, J. Jansen, J.-w. Jachtenberg, W. E. Visser, M. H. A. Kester, and T. J. Visser Effective Cellular Uptake and Efflux of Thyroid Hormone by Human Monocarboxylate Transporter 10 Mol. Endocrinol., June 1, 2008; 22(6): 1357 - 1369. [Abstract] [Full Text] [PDF]

				G. D. V. Sagar, B. Gereben, I. Callebaut, J.-P. Mornon, A. Zeold, C. Curcio-Morelli, J. W. Harney, C. Luongo, M. A. Mulcahey, P. R. Larsen, et al. The Thyroid Hormone-Inactivating Deiodinase Functions as a Homodimer Mol. Endocrinol., June 1, 2008; 22(6): 1382 - 1393. [Abstract] [Full Text] [PDF]

				E. Silvestri, A. Lombardi, P. de Lange, L. Schiavo, A. Lanni, F. Goglia, T. J. Visser, and M. Moreno Age-related changes in renal and hepatic cellular mechanisms associated with variations in rat serum thyroid hormone levels Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E1160 - E1168. [Abstract] [Full Text] [PDF]

				J. Jansen, E. C. H. Friesema, M. H. A. Kester, C. E. Schwartz, and T. J. Visser Genotype-Phenotype Relationship in Patients with Mutations in Thyroid Hormone Transporter MCT8 Endocrinology, May 1, 2008; 149(5): 2184 - 2190. [Abstract] [Full Text] [PDF]

				J. Jansen, E. C. H. Friesema, M. H. A. Kester, C. Milici, M. Reeser, A. Gruters, T. G. Barrett, E. E. Mancilla, J. Svensson, J.-L. Wemeau, et al. Functional Analysis of Monocarboxylate Transporter 8 Mutations Identified in Patients with X-Linked Psychomotor Retardation and Elevated Serum Triiodothyronine J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2378 - 2381. [Abstract] [Full Text] [PDF]