Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter
Open accessAbstract
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 approximately 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 microM 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.
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SLC16A2 encodes MCT8, a specific membrane transporter of TH, broadly expressed in the CNS.
“The solute carrier family 16, member 2 (SLC16A2) gene, located on the X chromosome, encodes monocarboxylate transporter 8 (MCT8), a specific membrane transporter of thyroid hormone (TH) (Friesema et al., 2003) broadly expressed in the central nervous system (CNS).”
From Modeling Psychomotor Retardation using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier (2017) · cites this paper as Friesema et al., 2003
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“Over the last two decades, clinical studies and experimental evidence have shown LT4 transporters including organic anion transporting polypeptide (OATP) family (20, 21), the Na-taurocholate co-transporting polypeptide (NTCP) (22), the L-type amino acid transporter 1 and 2 (LAT1 and LAT2) (23, 24), MCT8 (25) and MCT10…”
Background
- Authors
- Friesema, E. C. H., Ganguly, S., Abdalla, A., Fox, J. E. M., Halestrap, A. P., & Visser, T. J.
- Affiliations
- Erasmus MC (NL)
- University of Bristol (GB)
- Corresponding author
- Visser, Theo J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 278
- Issue
- 41
- Pages
- 40128-40135
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2160488497
- Cited by
- 725
- References
- 2
- Citations by year
- 2026: 24 · 2025: 25 · 2024: 32 · 2023: 22 · 2022: 29 · 2021: 45 · 2020: 28 · 2019: 43 · 2018: 16 · 2017: 31 · 2016: 41 · 2015: 31 · 2014: 43 · 2013: 43 · 2012: 26
- FWCI
- 17.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Explore Bristol Research (submittedVersion)
- Funders
- Wellcome Trust
- University of Bristol
- Medical Research Council
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chemical Analysis and Environmental Impact
- Keywords
- MCT8, SLC16A2, thyroid hormone transport, thyroxine uptake, triiodothyronine uptake, reverse T3, iodothyronines, amino acid transporters, transporter inhibition, albumin, tissue distribution, rats
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Biological Transport, Active, Cloning, Molecular, DNA, Female, Kinetics, Male, Molecular Sequence Data, Oocytes, Recombinant Proteins, Thyroid Hormones, Tissue Distribution, Xenopus laevis, Sequence Homology, Amino Acid, Monocarboxylic Acid Transporters, Rats, In Vitro Techniques
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