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Originally published In Press as doi:10.1074/jbc.M300909200 on July 18, 2003

J. Biol. Chem., Vol. 278, Issue 41, 40128-40135, October 10, 2003
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Identification of Monocarboxylate Transporter 8 as a Specific Thyroid Hormone Transporter*

Edith C. H. Friesema {ddagger} §, Sumita Ganguly § ¶ ||, Amal Abdalla {ddagger}, Jocelyn E. Manning Fox ¶ **, Andrew P. Halestrap ¶ and Theo J. Visser {ddagger} {ddagger}{ddagger}

From the {ddagger}Department of Internal Medicine, Erasmus University Medical Center, Rotterdam 3015 GE, The Netherlands and the Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom

Transport of thyroid hormone across the cell membrane is required for its action and metabolism. Recently, a T-type amino acid transporter was cloned which transports aromatic amino acids but not iodothyronines. This transporter belongs to the monocarboxylate transporter (MCT) family and is most homologous with MCT8 (SLC16A2). Therefore, we cloned rat MCT8 and tested it for thyroid hormone transport in Xenopus laevis oocytes. Oocytes were injected with rat MCT8 cRNA, and after 3 days immunofluorescence microscopy demonstrated expression of the protein at the plasma membrane. MCT8 cRNA induced an ~10-fold increase in uptake of 10 nM 125I-labeled thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3) and 3,3'-diiodothyronine. Because of the rapid uptake of the ligands, transport was only linear with time for <4 min. MCT8 did not transport Leu, Phe, Trp, or Tyr. [125I]T4 transport was strongly inhibited by L-T4, D-T4, L-T3, D-T3, 3,3',5-triiodothyroacetic acid, N-bromoacetyl-T3, and bromosulfophthalein. T3 transport was less affected by these inhibitors. Iodothyronine uptake in uninjected oocytes was reduced by albumin, but the stimulation induced by MCT8 was markedly increased. Saturation analysis provided apparent Km values of 2-5 µM for T4, T3, and rT3. Immunohistochemistry showed high expression in liver, kidney, brain, and heart. In conclusion, we have identified MCT8 as a very active and specific thyroid hormone transporter.

Received for publication, January 28, 2003 , and in revised form, July 10, 2003.

* This work was supported in part by a senior research leave fellowship from The Wellcome Trust (to A. P. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Both authors contributed equally to this work.

|| Supported by a University of Bristol postgraduate scholarship.

** Supported by a Medical Research Council research studentship.

{ddagger}{ddagger} To whom correspondence should be addressed: Dept. of Internal Medicine, Rm. Ee502, Erasmus University Medical Center, Dr. Molewaterplein 50, Rotterdam 3015 GE, The Netherlands. Tel.: 31-10-463-5463; Fax: 31-10-463-5430; E-mail: T.J.Visser{at}erasmusmc.nl.


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