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Importance of monocarboxylate transporter 8 for the blood-brain barrier-dependent availability of 3,5,3′-triiodo-L-thyronine
Open accessAbstract
Mutations of the gene expressing plasma membrane transporter for thyroid hormones MCT8 (SLC16A2) in humans lead to altered thyroid hormone levels and a severe neurodevelopmental disorder. Genetically engineered defect of the Mct8 gene in mice leads to similar thyroid hormone abnormalities but no obvious impairment of brain development or function. In this work we studied the relative role of the blood-brain barrier and the neuronal plasma cell membrane in the restricted access of T(3) to the target neurons. To this end we compared the effects of low doses of T(4) and T(3) on cerebellar structure and gene expression in wild-type (Wt) and Mct8 null male mice [Mct8-/y, knockout (KO)] made hypothyroid during the neonatal period. We found that compared with Wt animals, T(4) was considerably more potent than T(3) in the Mct8KO mice, indicating a restricted access of T(3), but not T(4), to neurons after systemic administration in vivo. In contrast, T(3) action in cultured cerebellar neurons was similar in Wt cells as in Mct8KO cells. The results suggest that the main restriction for T(3) entry into the neural target cells of the mouse deficient in Mct8 is at the blood-brain barrier.
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When Mct8 KO mice were made hypothyroid at neonatal stage, exogenous supplementation of T4, but not T3, rescued a mild phenotype in the cerebellum.
“When these mice were made hypothyroid at the neonatal stage, the exogenous supplementation of T4, but not T3, was able to rescue a mild phenotype in the cerebellum (Ceballos et al., 2009).”
From Modeling Psychomotor Retardation using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier (2017) · cites this paper as Ceballos et al., 2009
T4, but not T3, may cross the mouse MCT8-deficient BBB through a mouse-specific T4 transporter that is absent in human.
“This suggests that T4, but not T3, may cross the mouse MCT8-deficient blood-brain barrier (BBB) through the presence of a mouse-specific T4 transporter that is absent in human.”
From Modeling Psychomotor Retardation using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier (2017) · cites this paper as Ceballos et al., 2009
Murine Mct8 regulates the transport of T3 across the BBB.
“Murine Mct8 regulates the transport of T3 across the BBB (Ceballos et al., 2009; Mayerl et al., 2014)”
From Modeling Psychomotor Retardation using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier (2017) · cites this paper as Ceballos et al., 2009
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The type 2 iodothyronine deiodinase is expressed primarily in glial cells in the neonatal rat brain
Guadaño-Ferraz, A., Obregón, M. J., Germain, D. L. S., & Bernal, J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.19.10391 · Cited by 372
Self-citationAbnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8
Trajkovic, M., Visser, T. J., Mittag, J., Horn, S., Lukas, J., Darras, V. M., Raivich, G., Bauer, K., & Heuer, H. (2007) · Journal of Clinical Investigation · doi:10.1172/jci28253 · Cited by 353
Dumitrescu, A. M., Liao, X.-H., Weiss, R. E., Millen, K., & Refetoff, S. (2006) · Endocrinology · doi:10.1210/en.2006-0390 · Cited by 318
Self-citationHeuer, H., Maier, M. K., Iden, S., Mittag, J., Friesema, E. C. H., Visser, T. J., & Bauer, K. (2005) · Endocrinology · doi:10.1210/en.2004-1179 · Cited by 269
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Research works printed but not linked: 14
- Dumitrescu, 2004, A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene., Am J Hum Genet, 74, 168, 10.1086/380999 · DOI · Paper page
- Friesema, 2004, Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation., Lancet, 364, 1435, 10.1016/S0140-6736(04)17226-7 · DOI · Paper page
- Refetoff, 2007, Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination., Best Pract Res Clin Endocrinol Metab, 21, 277, 10.1016/j.beem.2007.03.005 · DOI
- Grüters, 2007, Thyroid hormone transporter defects., Endocr Dev, 10, 118
- Visser, 2008, Thyroid hormone transport in and out of cells., Trends Endocrinol Metab, 19, 50, 10.1016/j.tem.2007.11.003 · DOI
- Roberts, 2008, Expression of the thyroid hormone transporters MCT8 (SLC16A2) and OATP14 (SLCO1C1) at the blood-brain barrier., Endocrinology, 149, 6251, 10.1210/en.2008-0378 · DOI · Paper page
- Sugiyama, 2003, Functional characterization of rat brain-specific organic anion transporter (Oatp14) at the blood-brain barrier: high affinity transporter for thyroxine., J Biol Chem, 278, 43489, 10.1074/jbc.M306933200 · DOI · Paper page
- Boado, 1999, Selective expression of the large neutral amino acid transporter at the blood-brain barrier., Proc Natl Acad Sci USA, 96, 12079, 10.1073/pnas.96.21.12079 · DOI
- Bernal, 2002, Analysis of thyroid hormone-dependent genes in the brain by in situ hybridization., Methods Mol Biol, 202, 71
- Guadaño-Ferraz, 1999, Expression of type 2 iodothyronine deiodinase in hypothyroid rat brain indicates an important role of thyroid hormone in the development of specific primary sensory systems., J Neurosci, 19, 3430, 10.1523/JNEUROSCI.19-09-03430.1999 · DOI
- Manzano, 2003, Differential effects of triiodothyronine and the thyroid hormone receptor beta-specific agonist GC-1 on thyroid hormone target genes in the brain., Endocrinology, 144, 5480, 10.1210/en.2003-0633 · DOI
- Palha, 2002, Thyroid hormone distribution in the mouse brain: the role of transthyretin., Neuroscience, 113, 837, 10.1016/S0306-4522(02)00228-2 · DOI
- Blay, 1993, Transthyretin expression in the rat brain: effect of thyroid functional state and role in thyroxine transport., Brain Res, 632, 114, 10.1016/0006-8993(93)91145-I · DOI
- Dratman, 1991, Transport of iodothyronines from bloodstream to brain: contributions by blood:brain and choroid plexus:cerebrospinal fluid barriers., Brain Res, 554, 229, 10.1016/0006-8993(91)90194-Z · DOI
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Minireview: Thyroid Hormone Transporters: The Knowns and the Unknowns
Visser, W. E., Friesema, E. C. H., & Visser, T. J. (2011) · Molecular Endocrinology · doi:10.1210/me.2010-0095 · Cited by 390
Vatine, G. D., Al-Ahmad, A., Barriga, B. K., Svendsen, S., Salim, A., Garcia, L., Garcia, V. J., Ho, R., Yucer, N., Qian, T., et al. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2017.04.002 · Cited by 233
Self-citationGroeneweg, S., van Geest, F. S., Peeters, R. P., Heuer, H., & Visser, W. E. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnz008 · Cited by 216
Impact of Oatp1c1 deficiency on thyroid hormone metabolism and action in the mouse brain
Mayerl, S., Visser, T. J., Darras, V. M., Horn, S., & Heuer, H. (2012) · Endocrinology · doi:10.1210/en.2011-1633 · Cited by 138
Disorder of thyroid hormone transport into the tissues
Groeneweg, S., Visser, W. E., & Visser, T. J. (2017) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2017.05.001 · Cited by 75
Wittmann, G., Mohácsik, P., Balkhi, M. Y., Gereben, B., & Lechan, R. M. (2015) · Fluids and Barriers of the CNS · doi:10.1186/s12987-015-0016-8 · Cited by 43
“Recent knockout mouse models provided evidence that TH entry into the brain is largely dependent on two TH transporters, monocarboxylate transporter 8 (MCT8) and organic anion-transporting polypeptide 1c1 (OATP1c1) [4–9].”
BackgroundSoldin, O. P., Soldin, S. J., Vinks, A. A., Younis, I., & Landy, H. J. (2010) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0b013e3181f12fe5 · Cited by 9
Metadata
- Authors
- Ceballos, A., Belinchon, M. M., Sanchez-Mendoza, E., Grijota-Martinez, C., Dumitrescu, A. M., Refetoff, S., Morte, B., & Bernal, J.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Instituto de Investigaciones Biomedicas (A.C., M.M.B., E.S.-M., J.B.), Consejo Superior de Investigaciones Cientificas and Universidad Autonoma de Madrid, 28029 Madrid, Spain
- Center for Biomedical Research on Rare Diseases (C.G.-M., B.M., J.B.), 28029 Madrid, Spain
- University of Chicago (US)
- Corresponding author
- Morte, Beatriz
- Bernal, Juan
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2009-01-15
- Volume
- 150
- Issue
- 5
- Pages
- 2491-2496
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2671898
- OpenAlex
- W1976707420
- Cited by
- 173
- References
- 4
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 9 · 2023: 8 · 2022: 10 · 2021: 10 · 2020: 8 · 2019: 10 · 2018: 7 · 2017: 12 · 2016: 14 · 2015: 13 · 2014: 13 · 2013: 7 · 2012: 8
- FWCI
- 9.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- MCT8, SLC16A2, thyroid hormone transport, triiodothyronine, thyroxine, blood-brain barrier, hypothyroidism, cerebellar neurons, cerebellar development, neurodevelopmental disorders
- MeSH terms
- Animals, Animals, Newborn, Biological Transport, Blood-Brain Barrier, Cells, Cultured, Female, Male, Mice, Inbred C57BL, Neurons, Triiodothyronine, Mice, Knockout, Membrane Transport Proteins, Monocarboxylic Acid Transporters, Symporters, Mice, Neurogranin
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