Inhibition, monocarboxylate transporter 8 (MCT8)

Disruption of the thyroid hormone (TH) system is increasingly recognized as an important endocrine-disrupting mode of action, leading to numerous adverse effects across various vertebrate species. The two primary THs, thyroxine (T4) and 3,5,3’-triiodothyronine (T3), are iodinated derivatives of tyrosine secreted by the thyroid gland. Initially, it was thought that these lipophilic iodothyronines readily passed through the lipid bilayer of target cell membranes via simple passive diffusion. However, emerging research has highlighted the importance of specific, carrier-mediated transport mechanisms in regulating TH bioavailability (Hennemann et al., 2001; Visser, 2000). TH transmembrane transporters (THTMTs) are proteins that facilitate the uptake and/or efflux of THs across membranes of specific tissues and cells, thus modulating their biological effects. While the full complement of TH transporters remains uncertain, several families of THTMTs have been identified, including Na⁺-independent organic anion transporting polypeptides (OATP), large neutral amino acid transporters (LAT), ATP-binding cassette transporters (ABC), organic anion transporters (OAT), and monocarboxylate transporters (MCT) (Braunbeck & Lammer, 2006; Chen et al., 2023; Groeneweg et al., 2019; Hennemann et al., 2001; Visser, 2000).

Among these, MCTs have been the subject of the most extensive research. Specifically, MCT8 and MCT10 have been identified as proton-independent transporters of THs. Notably, MCT8 has been shown a key THTMT with high specificity, affinity and efficiency for THs, although its role in transporting others ligands cannot be excluded (Dierichs et al., 2025; Dumitrescu & Refetoff, 2013; Friesema et al., 2006; Fu et al., 2013; Heuer & Visser, 2009; Kinne et al., 2011; Lazcano et al., 2023; Maranduba et al., 2006; Noyes et al., 2019; van Geest et al., 2021; Vancamp & Darras, 2017, 2018; Zada et al., 2017).

The pivotal role of MCT8 as a THTMT has been revealed by mutations in the mct8 gene (SLC1642), which are associated with the X-linked mental retardation disorder Allan-Herndon-Dudley syndrome (AHDS) (Allan, 1944). This neurodevelopmental disorder has been characterized in humans by severe global developmental delays, cognitive impairments, and motor dysfunction (Dumitrescu et al., 2004; Friesema et al., 2004; Schwartz et al., 2005). Clinical and experimental studies have consistently linked MCT8 deficiency with impaired TH transport, resulting in a complex biological state marked by both peripheral hyperthyroidism and central hypothyroidism  ADDIN EN.CITE.DATA (Biebermann et al., 2005; Braun et al., 2012; Di Cosmo et al., 2010; Dierichs et al., 2025; Dumitrescu et al., 2006; Dumitrescu & Refetoff, 2013; Groeneweg, van Geest, et al., 2020; Jansen, 2008; Kinne et al., 2009; Kubota et al., 2022; Maity-Kumar et al., 2022; Mayerl et al., 2014; Salas-Lucia et al., 2024; Schweizer et al., 2014; Trajkovic et al., 2007; van Geest et al., 2021; Vancamp & Darras, 2017, 2018; Visser et al., 2008; Zada et al., 2017). The diagnostic hallmark of this syndrome includes elevated serum T3 levels, low-normal serum T4, and borderline-elevated thyroid-stimulating hormone (TSH) levels (peripheral hyperthyroidism). Tissues that rely on solely MCT8 for TH uptake, such as the brain, have been found to be in a hypothyroid state (central hypothyroidism), whereas peripheral tissues such as the liver, kidneys, and muscles – where other THTMTs may compensate for the absence of MCT8- reside in a hyperthyroid state. Other transporters that may contribute to TH transport in different tissues and circumstances include for example MCT10 and OATP1C1 (Wagenaars, 2025). However, the precise contributions of each individual transporter to overall TH distribution and regulation remains poorly understood.

In general, MCT8-mediated TH deficiency in the brain leads to significant neurological impairments and developmental issues, including intellectual disability, motor problems, speech difficulties, impaired brain maturation and function. Simultaneously, elevated TH levels in the peripheral tissues contribute to symptoms such as muscle wasting, tachycardia, and reduced body weight across various vertebrate species  ADDIN EN.CITE.DATA  ADDIN EN.CITE.DATA  ADDIN EN.CITE.DATA  ADDIN EN.CITE.DATA (Arjona et al., 2011; Biebermann et al., 2005; Brockmann et al., 2005; Campinho et al., 2014; Darras, 2019; de Vrieze et al., 2014; Delbaere et al., 2017a; Delbaere et al., 2017b; Dierichs et al., 2025; Dumitrescu et al., 2004; Dumitrescu & Refetoff, 2013; Fu et al., 2013; Gagliardi et al., 2015; Groeneweg et al., 2019; Groeneweg, van Geest, et al., 2020; Jansen, 2008; Kakinuma et al., 2005; Kubota et al., 2022; Lademann et al., 2022; Lazcano et al., 2023; Lee et al., 2017; Lopez-Espindola et al., 2014; Luongo et al., 2021; Maity-Kumar et al., 2022; Maranduba et al., 2006; Masnada et al., 2022; Mayerl & Heuer, 2023; Mayerl et al., 2014; Novara et al., 2017; Pagnin et al., 2021; Rozenblat et al., 2022; Schwartz et al., 2005; Sharlin et al., 2018; Silva & Campinho, 2023; Sterner et al., 2023; Tonduti et al., 2013; Valcarcel-Hernandez et al., 2022; van Geest et al., 2021; Vancamp & Darras, 2017, 2018; Vatine et al., 2013; Walter et al., 2019; Zada et al., 2017; Zada et al., 2016; Zada et al., 2014).

MCT8 exhibits a broad tissue distribution, with expression mostly observed in the liver, kidney, thyroid, pituitary, and brain, as well as in the heart, intestine, gut, placenta, and gills  ADDIN EN.CITE.DATA  ADDIN EN.CITE.DATA (Arjona et al., 2011; Bourgeois et al., 2016; Braun et al., 2011; Campinho et al., 2014; Choi et al., 2015; Connors et al., 2010; Delbaere et al., 2016; Di Cosmo et al., 2010; Dierichs et al., 2025; Friesema et al., 2003; Friesema et al., 2004; Fu et al., 2013; Geysens et al., 2012; Heuer et al., 2005; Heuer & Visser, 2009; Kakinuma et al., 2005; Maranduba et al., 2006; Nishimura & Naito, 2008; Salveridou et al., 2020; Trajkovic-Arsic et al., 2010; van Geest et al., 2021; Van Herck et al., 2015; Vancamp & Darras, 2017; Vancamp et al., 2017; Vatine et al., 2013; Visser et al., 2008; Yadav et al., 2022; Zada et al., 2017; Zada et al., 2016; Zada et al., 2014). Overall, MCT8 expression patterns are consistent across vertebrate species. However, the impact of MCT8 mutations on the function of different tissues may vary  depending on the reliance of specific tissues on MCT8 for TH uptake. For instance, in tissues like the liver, heart, and intestine, alternative transporters might contribute to TH supply. Additionally, MCT8 plays an essential role in TH efflux, particularly in the kidney and thyroid, where a hypothesized decrease in T4 efflux in the kidney and T4 secretion by the thyroid may occur. Expression of MCT8 in the pituitary and hypothalamus, in combination with normal TSDH levels, suggests that MCT8 mutations may affect TH negative feedback sensitivity. Finally, but probably most importantly, most research has been performed on MCT8 in brain tissues. The transporter has been shown to be a key regulator during neurodevelopment, with high expression in the central nervous system (CNS) already during early development (van Geest et al., 2021).

While the phenotype of MCT8 inhibition, by clinical genetic mutations/deficiencies or knock-down/-out animal studies, has been well-characterized (Bernal et al., 2015), less is known about the impact of chemical interference with MCT8. Given that several compounds have been identified in vitro as MCT8 inhibitors, exploring the potential toxicological implications of disrupting MCT8 function in vivo is an emerging priority in environmental research.

Currently, there are no OECD or EPA-approved guidelines available for measuring or detecting MCT8 inhibition, nor are there any available ToxCast assays for this purpose (Bernasconi et al., 2023; Dierichs et al., 2025). Given the high affinity and specificity of the MCT8 transporter for THs, it plays a crucial role in their uptake into target cells and organs. In light of its significance in TH signaling, the OECD has prioritized MCT8 inhibition as a key molecular target for which the development of screening assays should be expedited (OECD, 2014).

Some in vitro assays are available in literature that can be used to assess the inhibitory capacity of compounds on MCT8-mediated TH uptake. Early studies have examined the inhibition of T3 or T4 uptake into cells by measuring the uptake of radiolabeled T3/T4 into cultured cells, however without identification of the specific chemically inhibited transporter responsible for this uptake (Movius et al., 1989; Topliss et al., 1989). More recently, the use of cell lines expressing solely MCT8 as TH transporter has become a standard method to measure uptake of radiolabeled T3 or T4 into cells in culture. These assays typically employ either  MCT8-transfected Madin-Darby canine kidney (MDCK-1) cells (Braun et al., 2012; Braun & Schweizer, 2015; Johannes et al., 2016; Kinne et al., 2010; Kinne et al., 2009; Roth et al., 2010; Wirth et al., 2009) or MCT8-transfected Human Placenta Choriocarcinoma (JEG3) and African green monkey kidney fibroblast-like cells (COS1) cells (Chen et al., 2022; Groeneweg et al., 2013; Ianculescu et al., 2010). Although all mentioned cell lines have been used to identify potential MCT8 inhibitors, the JEG3 and COS1 cell lines were mostly transfected with (mutant) MCT8 for functional characterization of MCT8 (mutations) as TH transporter (Armour et al., 2015; Friesema et al., 2006; Groeneweg, van den Berge, et al., 2020; Jansen et al., 2007; Jansen et al., 2008; Kersseboom et al., 2013; Maranduba et al., 2006; Mughal et al., 2017; van Geest et al., 2020). However, due to challenges associated with handling, setup and regulatory difficulties with regards to the use of radiolabeled tracers, a non-radioactive, high-throughput screening assay was developed by Jayarama-Naidu et al. (2015). This spectrophotometric assay, based on the Sandell-Kolthoff reaction (Sandell & Kolthoff, 1937), measures T3 uptake by MDCK cells overexpressing human MCT8. In July 2017, the Joint Research Centre EU Reference Laboratory for Alternatives to Animal Testing (JRC EURL ECVAM) launched a validation study to assess a suite of 17 in vitro screening methods covering various TH- disrupting modes of action, including this non-radioactive method for MCT8 inhibition (Bernasconi et al., 2023). This simple, rapid and cost-effective method has already been proven in identifying potential endocrine-disrupting chemicals through MCT8 inhibition with high selectivity, specificity and reproducibility (Dong & Wade, 2017; Jayarama-Naidu et al., 2015; Johannes et al., 2016; Kadic et al., 2024; Wagenaars et al., 2024).

In vivo observations of MCT8 inhibition are typically indirect, relying on the impact of toxicants on TH levels, TH-related enzyme activities, and/or downstream effects. Since toxicants can target multiple molecular components along the TH axis, interpretating serum TH concentrations may prove difficult. Furthermore, serum TH concentrations may not always correlate with brain TH status (O'Shaughnessy & Gilbert, 2020). While detection of TH distribution via LC-MS/MS is probably the best and most advanced approach for quantitative and qualitative assessment of multiple THs, it requires a high level of hands-on skills and costly equipment (De Angelis et al., 2022; Kinne et al., 2010).

Using these in vitro (and/or in vivo) assays, several MCT8 inhibitors have been identified. These include desipramine, bromosulfophtalein, genistein, several tyrosine kinase inhibitors, silychristin, p-chloromercurybenzensulfonate, mercury(II)chloride, cardiogreen, meclofenamic acid, phloretin, bisphenol A, dexamethasone, buspirone,  dronedarone, desethylamiodarone, methylmercury, bisphenol-AF and bisphenol Z (Braun et al., 2012; Braun & Schweizer, 2015; Di Cosmo et al., 2022; Dong & Wade, 2017; Jayarama-Naidu et al., 2015; Johannes et al., 2016; Kinne et al., 2009; Lima de Souza et al., 2013; Roth et al., 2010; Sardarova et al., 2025; Wagenaars et al., 2024; Wagenaars, 2025; Wirth et al., 2009).

Taxonomic: MCT8 has been identified and characterized in multiple vertebrate species, with high sequence homology and conserved gene structure across these taxonomic groups. This conservation is supported by data from human clinical studies and experiments using animal models including mammals (mice, rats), birds (chickens), amphibians (Xenopus), and fish (zebrafish)  ADDIN EN.CITE.DATA (Arjona et al., 2011; Bourgeois et al., 2016; Campinho et al., 2014; Delbaere et al., 2017a; Dierichs et al., 2025; Dumitrescu et al., 2004; Dumitrescu & Refetoff, 2013; Friesema et al., 2003; Fu et al., 2013; Jansen et al., 2005; Lazcano et al., 2023; Sterner et al., 2023; van Geest et al., 2021; Vancamp & Darras, 2017, 2018; Vatine et al., 2013; Visser et al., 2011; Zada et al., 2017). MCT8 appears to be conserved in structure, protein sequence, function in TH transport, and anatomical localization across these species. While MCT8 is well-studied in vertebrates, information on MCT8 (inhibition) in invertebrates is scarce. Only a few studies have identified a homologous mct8 gene in invertebrates, such as the purple sea urchin (Cocurullo et al., 2023), but the functional relevance of MCT8 in TH transport in invertebrates remains unconfirmed. Therefore, this molecular initiating event (MIE) is primarily applicable across vertebrate species.

Despite broad conservation, particularly the transmembrane domains of MCT8 (Fu & Dumitrescu, 2014), small differences in gene structure have been identified among species. For example, non-primate MCT8 genes lack the upstream translation start site present in humans (Jansen et al., 2005), and zebrafish MCT8 contains a single N-terminal PEST domain, whereas humans have three (Arjona et al., 2011).  The functional implications of these variations remain unclear.

While MCT8’s overall function in TH transport seems to be highly conserved, species-specific differences may arise due to specific cellular context or the presence of other transporters. Vancamp and Darras (2018) reviewed the expression of the MCT8, OATP and LAT transporters in humans, mice, chickens, and zebrafish, highlighting key interspecies differences (Dierichs et al., 2025; Vancamp & Darras, 2018). For instance, mice and zebrafish have an additional OATP-mediated T4 transport capacity at the blood-brain-barrier (BBB), which is absent in humans, while chickens lack MCT8 expression at the BBB (Bourgeois et al., 2016; Delbaere et al., 2016; Friesema et al., 2004; Geysens et al., 2012; Trajkovic-Arsic et al., 2010; Van Herck et al., 2015; Vancamp & Darras, 2017, 2018; Visser et al., 2008; Wagenaars, 2025).

With regards to the species-specific adverse outcomes of MCT8 inhibition, it should be mentioned that empirical toxicological in vivo evidence that chemical exposure to MCT8-inhibitors, and THTMT inhibitors in general, may lead to adverse health outcomes, is very limited. Furthermore, if these chemicals affected in vivo TH levels, it remains uncertain whether these changes are caused by MCT8 inhibition specifically, or by interference with other components of the TH axis, such as TH synthesis or metabolism (Basolo et al., 2022; Campos-Barros et al., 1995; Illouz et al., 2014; Szkudelska & Nogowski, 2007). Most data originates from clinical studies with MCT8 mutations in humans and/or knock-out/-down studies in vertebrate animal models. Depending on the type of mutation, this results in partial to complete loss of MCT8 function, a situation that may be mimicked by chemical exposure to MCT8 inhibitors (Dumitrescu & Refetoff, 2013; Fu & Dumitrescu, 2014; Grijota-Martinez et al., 2020).

Although various animal models provide valuable insights into MCT8 deficiency, interspecies differences—especially in neurological outcomes— highlight the need for caution when extrapolating findings to human. Zebrafish appear to best replicate the human CNS impairments seen in AHDS, despite limited data on cognition and adult behavior, while mice, chickens, and amphibians often only show peripheral or limited CNS effects due to compensatory mechanisms (Vancamp & Darras, 2018).

Even though species-specific differences in gene structure, expression, function and adverse implications may exist, the overall importance and conservation of MCT8 in TH transport and signaling across vertebrate species is well-established.

Allan, W. H., C.C., Dudley, F.C. . (1944). Some examples of the inheritance of mental deficiency: apparently sex-linked idiocy and microcephaly. American Journal of Mental Deficiency, 48, 325-334.

Arjona, F. J., de Vrieze, E., Visser, T. J., Flik, G., & Klaren, P. H. (2011). Identification and functional characterization of zebrafish solute carrier Slc16a2 (Mct8) as a thyroid hormone membrane transporter. Endocrinology, 152(12), 5065-5073. https://doi.org/10.1210/en.2011-1166

Armour, C. M., Kersseboom, S., Yoon, G., & Visser, T. J. (2015). Further Insights into the Allan-Herndon-Dudley Syndrome: Clinical and Functional Characterization of a Novel MCT8 Mutation. PLoS One, 10(10), e0139343. https://doi.org/10.1371/journal.pone.0139343

Basolo, A., Matrone, A., Elisei, R., & Santini, F. (2022). Effects of tyrosine kinase inhibitors on thyroid function and thyroid hormone metabolism. Semin Cancer Biol, 79, 197-202. https://doi.org/10.1016/j.semcancer.2020.12.008

Bernal, J., Guadaño-Ferraz, A., & Morte, B. (2015). Thyroid hormone transporters—functions and clinical implications. Nature Reviews Endocrinology, 11(7), 406-417. https://doi.org/10.1038/nrendo.2015.66

Bernasconi, C., Bartnicka, J., Asturiol, D., Bowe, G., Langezaal, I., Coecke, S., Kienzler, A., Liska, R., Milcamps, A., & Munoz Pineiro, A. (2023). Validation of a battery of mechanistic methods relevant for the detection of chemicals that can disrupt the thyroid hormone system. Luxembourg: Publications Office of the European Union. doi, 10, 862948.

Biebermann, H., Ambrugger, P., Tarnow, P., von Moers, A., Schweizer, U., & Grueters, A. (2005). Extended clinical phenotype, endocrine investigations and functional studies of a loss-of-function mutation A150V in the thyroid hormone specific transporter MCT8. Eur J Endocrinol, 153(3), 359-366. https://doi.org/10.1530/eje.1.01980

Bourgeois, N. M., Van Herck, S. L., Vancamp, P., Delbaere, J., Zevenbergen, C., Kersseboom, S., Darras, V. M., & Visser, T. J. (2016). Characterization of Chicken Thyroid Hormone Transporters. Endocrinology, 157(6), 2560-2574. https://doi.org/10.1210/en.2015-2025

Braun, D., Kim, T. D., le Coutre, P., Kohrle, J., Hershman, J. M., & Schweizer, U. (2012). Tyrosine kinase inhibitors noncompetitively inhibit MCT8-mediated iodothyronine transport. J Clin Endocrinol Metab, 97(1), E100-105. https://doi.org/10.1210/jc.2011-1837

Braun, D., Kinne, A., Brauer, A. U., Sapin, R., Klein, M. O., Kohrle, J., Wirth, E. K., & Schweizer, U. (2011). Developmental and cell type-specific expression of thyroid hormone transporters in the mouse brain and in primary brain cells. Glia, 59(3), 463-471. https://doi.org/10.1002/glia.21116

Braun, D., & Schweizer, U. (2015). Efficient Activation of Pathogenic DeltaPhe501 Mutation in Monocarboxylate Transporter 8 by Chemical and Pharmacological Chaperones. Endocrinology, 156(12), 4720-4730. https://doi.org/10.1210/en.2015-1393

Braunbeck, T., & Lammer, E. (2006). Detailed review paper "fish embryo toxicity assays. UBA Report under Contract.

Brockmann, K., Dumitrescu, A. M., Best, T. T., Hanefeld, F., & Refetoff, S. (2005). X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene. J Neurol, 252(6), 663-666. https://doi.org/10.1007/s00415-005-0713-3

Campinho, M. A., Saraiva, J., Florindo, C., & Power, D. M. (2014). Maternal thyroid hormones are essential for neural development in zebrafish. Mol Endocrinol, 28(7), 1136-1149. https://doi.org/10.1210/me.2014-1032

Campos-Barros, A., Meinhold, H., Köhler, R., Müller, F., Eravci, M., & Baumgartner, A. (1995). The effects of desipramine on thyroid hormone concentrations in rat brain. Naunyn-Schmiedeberg's Archives of Pharmacology, 351(5), 469-474. https://doi.org/10.1007/BF00171037

Chen, Z., Peeters, R. P., Flach, W., de Rooij, L. J., Yildiz, S., Teumer, A., Nauck, M., Sterenborg, R. B. T. M., Rutten, J. H. W., Medici, M., Edward Visser, W., & Meima, M. E. (2023). Novel (sulfated) thyroid hormone transporters in the solute carrier 22 family. European Thyroid Journal, 12(4), e230023. https://doi.org/10.1530/etj-23-0023

Chen, Z., van der Sman, A. S. E., Groeneweg, S., de Rooij, L. J., Visser, W. E., Peeters, R. P., & Meima, M. E. (2022). Thyroid Hormone Transporters in a Human Placental Cell Model. Thyroid®, 32(9), 1129-1137. https://doi.org/10.1089/thy.2021.0503

Choi, J., Moskalik, C. L., Ng, A., Matter, S. F., & Buchholz, D. R. (2015). Regulation of thyroid hormone-induced development in vivo by thyroid hormone transporters and cytosolic binding proteins. Gen Comp Endocrinol, 222, 69-80. https://doi.org/10.1016/j.ygcen.2015.07.006

Cocurullo, M., Paganos, P., Wood, N. J., Arnone, M. I., & Oliveri, P. (2023). Molecular and Cellular Characterization of the TH Pathway in the Sea Urchin Strongylocentrotus purpuratus. Cells, 12(2). https://doi.org/10.3390/cells12020272

Connors, K. A., Korte, J. J., Anderson, G. W., & Degitz, S. J. (2010). Characterization of thyroid hormone transporter expression during tissue-specific metamorphic events in Xenopus tropicalis. Gen Comp Endocrinol, 168(1), 149-159. https://doi.org/10.1016/j.ygcen.2010.04.015

Darras, V. M. (2019). The Role of Maternal Thyroid Hormones in Avian Embryonic Development. Front Endocrinol (Lausanne), 10, 66. https://doi.org/10.3389/fendo.2019.00066

De Angelis, M., Maity-Kumar, G., Schriever, S. C., Kozlova, E. V., Müller, T. D., Pfluger, P. T., Curras-Collazo, M. C., & Schramm, K. W. (2022). Development and validation of an LC-MS/MS methodology for the quantification of thyroid hormones in dko MCT8/OATP1C1 mouse brain. J Pharm Biomed Anal, 221, 115038. https://doi.org/10.1016/j.jpba.2022.115038

de Vrieze, E., van de Wiel, S. M., Zethof, J., Flik, G., Klaren, P. H., & Arjona, F. J. (2014). Knockdown of monocarboxylate transporter 8 (mct8) disturbs brain development and locomotion in zebrafish. Endocrinology, 155(6), 2320-2330. https://doi.org/10.1210/en.2013-1962

Delbaere, J., Van Herck, S. L. J., Bourgeois, N. M. A., Vancamp, P., Yang, S., Wingate, R. J. T., & Darras, V. M. (2016). Mosaic Expression of Thyroid Hormone Regulatory Genes Defines Cell Type-Specific Dependency in the Developing Chicken Cerebellum. The Cerebellum, 15(6), 710-725. https://doi.org/10.1007/s12311-015-0744-y

Delbaere, J., Vancamp, P., Van Herck, S. L., Bourgeois, N. M., Green, M. J., Wingate, R. J., & Darras, V. M. (2017a). MCT8 deficiency in Purkinje cells disrupts embryonic chicken cerebellar development. J Endocrinol, 232(2), 259-272. https://doi.org/10.1530/JOE-16-0323

Delbaere, J., Vancamp, P., Van Herck, S. L. J., Bourgeois, N. M. A., Green, M. J., Wingate, R. J. T., & Darras, V. M. (2017b). MCT8 deficiency in Purkinje cells disrupts embryonic chicken cerebellar development [Article]. Journal of Endocrinology, 232(2), 259-272. https://doi.org/10.1530/JOE-16-0323

Di Cosmo, C., De Marco, G., Agretti, P., Ferrarini, E., Dimida, A., Falcetta, P., Benvenga, S., Vitti, P., & Tonacchera, M. (2022). Screening for drugs potentially interfering with MCT8-mediated T(3) transport in vitro identifies dexamethasone and some commonly used drugs as inhibitors of MCT8 activity. J Endocrinol Invest, 45(4), 803-814. https://doi.org/10.1007/s40618-021-01711-4

Di Cosmo, C., Liao, X. H., Dumitrescu, A. M., Philp, N. J., Weiss, R. E., & Refetoff, S. (2010). Mice deficient in MCT8 reveal a mechanism regulating thyroid hormone secretion. J Clin Invest, 120(9), 3377-3388. https://doi.org/10.1172/JCI42113

Dierichs, N. T. O. M., H., P. A., P., P. R., Edward, V. W., E., M. M., & and Hessel, E. V. S. (2025). Mechanisms of developmental neurotoxicity mediated by perturbed thyroid hormone homeostasis in the brain: an adverse outcome pathway network. Critical Reviews in Toxicology, 55(3), 304-320. https://doi.org/10.1080/10408444.2025.2461076

Dong, H., & Wade, M. G. (2017). Application of a nonradioactive assay for high throughput screening for inhibition of thyroid hormone uptake via the transmembrane transporter MCT8. Toxicol In Vitro, 40, 234-242. https://doi.org/10.1016/j.tiv.2017.01.014

Dumitrescu, A. M., Liao, X.-H., Best, T. B., Brockmann, K., & Refetoff, S. (2004). A Novel Syndrome Combining Thyroid and Neurological Abnormalities Is Associated with Mutations in a Monocarboxylate Transporter Gene. The American Journal of Human Genetics, 74(1), 168-175. https://doi.org/https://doi.org/10.1086/380999

Dumitrescu, A. M., Liao, X. H., Weiss, R. E., Millen, K., & Refetoff, S. (2006). Tissue-specific thyroid hormone deprivation and excess in monocarboxylate transporter (mct) 8-deficient mice. Endocrinology, 147(9), 4036-4043. https://doi.org/10.1210/en.2006-0390

Dumitrescu, A. M., & Refetoff, S. (2013). The syndromes of reduced sensitivity to thyroid hormone. Biochim Biophys Acta, 1830(7), 3987-4003. https://doi.org/10.1016/j.bbagen.2012.08.005

Friesema, E. C., Ganguly, S., Abdalla, A., Manning Fox, J. E., Halestrap, A. P., & Visser, T. J. (2003). Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem, 278(41), 40128-40135. https://doi.org/10.1074/jbc.M300909200

Friesema, E. C., Grueters, A., Biebermann, H., Krude, H., von Moers, A., Reeser, M., Barrett, T. G., Mancilla, E. E., Svensson, J., Kester, M. H., Kuiper, G. G., Balkassmi, S., Uitterlinden, A. G., Koehrle, J., Rodien, P., Halestrap, A. P., & Visser, T. J. (2004). Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet, 364(9443), 1435-1437. https://doi.org/10.1016/S0140-6736(04)17226-7

Friesema, E. C. H., Kuiper, G. G. J. M., Jansen, J., Visser, T. J., & Kester, M. H. A. (2006). Thyroid Hormone Transport by the Human Monocarboxylate Transporter 8 and Its Rate-Limiting Role in Intracellular Metabolism. Molecular Endocrinology, 20(11), 2761-2772. https://doi.org/10.1210/me.2005-0256

Fu, J., & Dumitrescu, A. M. (2014). Inherited defects in thyroid hormone cell-membrane transport and metabolism. Best Pract Res Clin Endocrinol Metab, 28(2), 189-201. https://doi.org/10.1016/j.beem.2013.05.014

Fu, J., Refetoff, S., & Dumitrescu, A. M. (2013). Inherited defects of thyroid hormone-cell-membrane transport: review of recent findings. Curr Opin Endocrinol Diabetes Obes, 20(5), 434-440. https://doi.org/10.1097/01.med.0000432531.03233.ad

Gagliardi, L., Nataren, N., Feng, J., Schreiber, A. W., Hahn, C. N., Conwell, L. S., Coman, D., & Scott, H. S. (2015). Allan-Herndon-Dudley syndrome with unusual profound sensorineural hearing loss. Am J Med Genet A, 167A(8), 1872-1876. https://doi.org/10.1002/ajmg.a.37075

Geysens, S., Ferran, J. L., Van Herck, S. L., Tylzanowski, P., Puelles, L., & Darras, V. M. (2012). Dynamic mRNA distribution pattern of thyroid hormone transporters and deiodinases during early embryonic chicken brain development. Neuroscience, 221, 69-85. https://doi.org/10.1016/j.neuroscience.2012.06.057

Grijota-Martinez, C., Barez-Lopez, S., Gomez-Andres, D., & Guadano-Ferraz, A. (2020). MCT8 Deficiency: The Road to Therapies for a Rare Disease. Front Neurosci, 14, 380. https://doi.org/10.3389/fnins.2020.00380

Groeneweg, S., Lima de Souza, E. C., Visser, W. E., Peeters, R. P., & Visser, T. J. (2013). Importance of His192 in the Human Thyroid Hormone Transporter MCT8 for Substrate Recognition. Endocrinology, 154(7), 2525-2532. https://doi.org/10.1210/en.2012-2225

Groeneweg, S., Peeters, R. P., Moran, C., Stoupa, A., Auriol, F., Tonduti, D., Dica, A., Paone, L., Rozenkova, K., Malikova, J., van der Walt, A., de Coo, I. F. M., McGowan, A., Lyons, G., Aarsen, F. K., Barca, D., van Beynum, I. M., van der Knoop, M. M., Jansen, J.,…Visser, W. E. (2019). Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial. Lancet Diabetes Endocrinol, 7(9), 695-706. https://doi.org/10.1016/S2213-8587(19)30155-X

Groeneweg, S., van den Berge, A., Lima de Souza, E. C., Meima, M. E., Peeters, R. P., & Visser, W. E. (2020). Insights Into the Mechanism of MCT8 Oligomerization. J Endocr Soc, 4(8), bvaa080. https://doi.org/10.1210/jendso/bvaa080

Groeneweg, S., van Geest, F. S., Abaci, A., Alcantud, A., Ambegaonkar, G. P., Armour, C. M., Bakhtiani, P., Barca, D., Bertini, E. S., van Beynum, I. M., Brunetti-Pierri, N., Bugiani, M., Cappa, M., Cappuccio, G., Castellotti, B., Castiglioni, C., Chatterjee, K., de Coo, I. F. M., Coutant, R.,…Visser, W. E. (2020). Disease characteristics of MCT8 deficiency: an international, retrospective, multicentre cohort study. Lancet Diabetes Endocrinol, 8(7), 594-605. https://doi.org/10.1016/S2213-8587(20)30153-4

Groeneweg, S., van Geest, F. S., van der Most, F., Abela, L., Alfieri, P., Bauer, A. J., Bertini, E., Cappa, M., Çelik, N., de Coo, I. F. M., Dolcetta-Capuzzo, A., Dubinski, I., Granadillo, J. L., Hoefsloot, L. H., Kalscheuer, V. M., van der Knoop, M. M., Krude, H., McNerney, K. P., Paone, L.,…Visser, W. E. (2025). MCT8 Deficiency in Females. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/clinem/dgaf311

Hennemann, G., Docter, R., Friesema, E. C. H., de Jong, M., Krenning, E. P., & Visser, T. J. (2001). Plasma Membrane Transport of Thyroid Hormones and Its Role in Thyroid Hormone Metabolism and Bioavailability. Endocrine Reviews, 22(4), 451-476. https://doi.org/10.1210/edrv.22.4.0435

Heuer, H., Maier, M. K., Iden, S., Mittag, J., Friesema, E. C., Visser, T. J., & Bauer, K. (2005). The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations. Endocrinology, 146(4), 1701-1706. https://doi.org/10.1210/en.2004-1179

Heuer, H., & Visser, T. J. (2009). Minireview: Pathophysiological importance of thyroid hormone transporters. Endocrinology, 150(3), 1078-1083. https://doi.org/10.1210/en.2008-1518

Ianculescu, A. G., Friesema, E. C. H., Visser, T. J., Giacomini, K. M., & Scanlan, T. S. (2010). Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine [10.1039/B926588K]. Molecular BioSystems, 6(8), 1403-1410. https://doi.org/10.1039/B926588K

Illouz, F., Braun, D., Briet, C., Schweizer, U., & Rodien, P. (2014). ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: Thyroid effects of tyrosine kinase inhibitors. European Journal of Endocrinology, 171(3), R91-R99. https://doi.org/10.1530/eje-14-0198

Jansen, J. (2008). Mutations in Thyroid Hormone Transporter MCT8: genotype, function and phenotype Erasmus Universiteit Rotterdam]. Amsterdam.

Jansen, J., Friesema, E. C., Kester, M. H., Milici, C., Reeser, M., Gruters, A., Barrett, T. G., Mancilla, E. E., Svensson, J., Wemeau, J. L., Busi da Silva Canalli, M. H., Lundgren, J., McEntagart, M. E., Hopper, N., Arts, W. F., & Visser, T. J. (2007). Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine. J Clin Endocrinol Metab, 92(6), 2378-2381. https://doi.org/10.1210/jc.2006-2570

Jansen, J., Friesema, E. C., Kester, M. H., Schwartz, C. E., & Visser, T. J. (2008). Genotype-phenotype relationship in patients with mutations in thyroid hormone transporter MCT8. Endocrinology, 149(5), 2184-2190. https://doi.org/10.1210/en.2007-1475

Jansen, J., Friesema, E. C. H., Milici, C., & Visser, T. J. (2005). Thyroid Hormone Transporters in Health and Disease. Thyroid®, 15(8), 757-768. https://doi.org/10.1089/thy.2005.15.757

Jayarama-Naidu, R., Johannes, J., Meyer, F., Wirth, E. K., Schomburg, L., Kohrle, J., & Renko, K. (2015). A Nonradioactive Uptake Assay for Rapid Analysis of Thyroid Hormone Transporter Function. Endocrinology, 156(7), 2739-2745. https://doi.org/10.1210/en.2015-1016

Johannes, J., Jayarama-Naidu, R., Meyer, F., Wirth, E. K., Schweizer, U., Schomburg, L., Kohrle, J., & Renko, K. (2016). Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8. Endocrinology, 157(4), 1694-1701. https://doi.org/10.1210/en.2015-1933

Kadic, A., Oles, P., Fischer, B. C., Reetz, A. E., Sylla, B. S., Feiertag, K., Ritz, V., Heise, T., Marx-Stoelting, P., Tralau, T., Renko, K., & Solano, M. d. L. M. (2024). In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles. Scientific Reports, 14(1), 6503. https://doi.org/10.1038/s41598-024-55019-3

Kakinuma, H., Itoh, M., & Takahashi, H. (2005). A novel mutation in the monocarboxylate transporter 8 gene in a boy with putamen lesions and low free T4 levels in cerebrospinal fluid. J Pediatr, 147(4), 552-554. https://doi.org/10.1016/j.jpeds.2005.05.012

Kersseboom, S., Kremers, G. J., Friesema, E. C., Visser, W. E., Klootwijk, W., Peeters, R. P., & Visser, T. J. (2013). Mutations in MCT8 in patients with Allan-Herndon-Dudley-syndrome affecting its cellular distribution. Mol Endocrinol, 27(5), 801-813. https://doi.org/10.1210/me.2012-1356

Kinne, A., Kleinau, G., Hoefig, C. S., Grüters, A., Köhrle, J., Krause, G., & Schweizer, U. (2010). Essential molecular determinants for thyroid hormone transport and first structural implications for monocarboxylate transporter 8. J Biol Chem, 285(36), 28054-28063. https://doi.org/10.1074/jbc.M110.129577

Kinne, A., Roth, S., Biebermann, H., Köhrle, J., Grüters, A., & Schweizer, U. (2009). Surface translocation and tri-iodothyronine uptake of mutant MCT8 proteins are cell type-dependent. Journal of Molecular Endocrinology, 43(6), 263-271. https://doi.org/10.1677/jme-09-0043

Kinne, A., Schülein, R., & Krause, G. (2011). Primary and secondary thyroid hormone transporters. Thyroid Research, 4(1), S7. https://doi.org/10.1186/1756-6614-4-S1-S7

Kubota, M., Yakuwa, A., Terashima, H., & Hoshino, H. (2022). A nationwide survey of monocarboxylate transporter 8 deficiency in Japan: Its incidence, clinical course, MRI and laboratory findings. Brain Dev, 44(10), 699-705. https://doi.org/10.1016/j.braindev.2022.07.007

Lademann, F., Tsourdi, E., Hofbauer, L. C., & Rauner, M. (2022). Bone cell-specific deletion of thyroid hormone transporter Mct8 distinctly regulates bone volume in young versus adult male mice. Bone, 159, 116375. https://doi.org/10.1016/j.bone.2022.116375

Lazcano, I., Pech-Pool, S. M., Olvera, A., Garcia-Martinez, I., Palacios-Perez, S., & Orozco, A. (2023). The importance of thyroid hormone signaling during early development: Lessons from the zebrafish model. Gen Comp Endocrinol, 334, 114225. https://doi.org/10.1016/j.ygcen.2023.114225

Lee, J. Y., Kim, M. J., Deliyanti, D., Azari, M. F., Rossello, F., Costin, A., Ramm, G., Stanley, E. G., Elefanty, A. G., Wilkinson-Berka, J. L., & Petratos, S. (2017). Overcoming Monocarboxylate Transporter 8 (MCT8)-Deficiency to Promote Human Oligodendrocyte Differentiation and Myelination. EBioMedicine, 25, 122-135. https://doi.org/10.1016/j.ebiom.2017.10.016

Lima de Souza, E. C., Groeneweg, S., Visser, W. E., Peeters, R. P., & Visser, T. J. (2013). Importance of Cysteine Residues in the Thyroid Hormone Transporter MCT8. Endocrinology, 154(5), 1948-1955. https://doi.org/10.1210/en.2012-2101

Lopez-Espindola, D., Morales-Bastos, C., Grijota-Martinez, C., Liao, X. H., Lev, D., Sugo, E., Verge, C. F., Refetoff, S., Bernal, J., & Guadano-Ferraz, A. (2014). Mutations of the thyroid hormone transporter MCT8 cause prenatal brain damage and persistent hypomyelination. J Clin Endocrinol Metab, 99(12), E2799-2804. https://doi.org/10.1210/jc.2014-2162

Luongo, C., Butruille, L., Sebillot, A., Le Blay, K., Schwaninger, M., Heuer, H., Demeneix, B. A., & Remaud, S. (2021). Absence of Both Thyroid Hormone Transporters MCT8 and OATP1C1 Impairs Neural Stem Cell Fate in the Adult Mouse Subventricular Zone. Stem Cell Reports, 16(2), 337-353. https://doi.org/10.1016/j.stemcr.2020.12.009

Maity-Kumar, G., Stander, L., DeAngelis, M., Lee, S., Molenaar, A., Becker, L., Garrett, L., Amerie, O. V., Hoelter, S. M., Wurst, W., Fuchs, H., Feuchtinger, A., Gailus-Durner, V., Garcia-Caceres, C., Othman, A. E., Brockmann, C., Schoffling, V. I., Beiser, K., Krude, H.,…Muller, T. D. (2022). Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome. Mol Metab, 66, 101616. https://doi.org/10.1016/j.molmet.2022.101616

Maranduba, C. M., Friesema, E. C., Kok, F., Kester, M. H., Jansen, J., Sertie, A. L., Passos-Bueno, M. R., & Visser, T. J. (2006). Decreased cellular uptake and metabolism in Allan-Herndon-Dudley syndrome (AHDS) due to a novel mutation in the MCT8 thyroid hormone transporter. J Med Genet, 43(5), 457-460. https://doi.org/10.1136/jmg.2005.035840

Masnada, S., Sarret, C., Antonello, C. E., Fadilah, A., Krude, H., Mura, E., Mordekar, S., Nicita, F., Olivotto, S., Orcesi, S., Porta, F., Remerand, G., Siri, B., Wilpert, N. M., Amir-Yazdani, P., Bertini, E., Schuelke, M., Bernard, G., Boespflug-Tanguy, O., & Tonduti, D. (2022). Movement disorders in MCT8 deficiency/Allan-Herndon-Dudley Syndrome. Mol Genet Metab, 135(1), 109-113. https://doi.org/10.1016/j.ymgme.2021.12.003

Mayerl, S., & Heuer, H. (2023). Thyroid hormone transporter Mct8/Oatp1c1 deficiency compromises proper oligodendrocyte maturation in the mouse CNS. Neurobiol Dis, 184, 106195. https://doi.org/10.1016/j.nbd.2023.106195

Mayerl, S., Muller, J., Bauer, R., Richert, S., Kassmann, C. M., Darras, V. M., Buder, K., Boelen, A., Visser, T. J., & Heuer, H. (2014). Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. J Clin Invest, 124(5), 1987-1999. https://doi.org/10.1172/JCI70324

Movius, E. G., Phyillaier, M. M., & Robbins, J. (1989). Phloretin Inhibits Cellular Uptake and Nuclear Receptor Binding of Triiodothyronine in Human Hep G2 Hepatocarcinoma Cells*. Endocrinology, 124(4), 1988-1997. https://doi.org/10.1210/endo-124-4-1988

Mughal, B. B., Leemans, M., Lima de Souza, E. C., le Mevel, S., Spirhanzlova, P., Visser, T. J., Fini, J. B., & Demeneix, B. A. (2017). Functional Characterization of Xenopus Thyroid Hormone Transporters mct8 and oatp1c1. Endocrinology, 158(8), 2694-2705. https://doi.org/10.1210/en.2017-00108

Nishimura, M., & Naito, S. (2008). Tissue-specific mRNA expression profiles of human solute carrier transporter superfamilies. Drug Metab Pharmacokinet, 23(1), 22-44. https://doi.org/10.2133/dmpk.23.22

Novara, F., Groeneweg, S., Freri, E., Estienne, M., Reho, P., Matricardi, S., Castellotti, B., Visser, W. E., Zuffardi, O., & Visser, T. J. (2017). Clinical and Molecular Characteristics of SLC16A2 (MCT8) Mutations in Three Families with the Allan-Herndon-Dudley Syndrome. Hum Mutat, 38(3), 260-264. https://doi.org/10.1002/humu.23140

Noyes, P. D., Friedman, K. P., Browne, P., Haselman, J. T., Gilbert, M. E., Hornung, M. W., Barone, S., Crofton, K. M., Laws, S. C., Stoker, T. E., Simmons, S. O., Tietge, J. E., & Degitz, S. J. (2019). Evaluating Chemicals for Thyroid Disruption: Opportunities and Challenges with <i>in Vitro</i> Testing and Adverse Outcome Pathway Approaches. Environmental Health Perspectives, 127(9), 095001. https://doi.org/doi:10.1289/EHP5297

O'Shaughnessy, K. L., & Gilbert, M. E. (2020). Thyroid disrupting chemicals and developmental neurotoxicity – New tools and approaches to evaluate hormone action. Molecular and Cellular Endocrinology, 518, 110663. https://doi.org/https://doi.org/10.1016/j.mce.2019.110663

OECD. (2014). New Scoping Document on in vitro and ex vivo Assays for the Identification of Modulators of Thyroid Hormone Signalling. https://doi.org/doi:https://doi.org/10.1787/9789264274716-en

Pagnin, M., Kondos-Devcic, D., Chincarini, G., Cumberland, A., Richardson, S. J., & Tolcos, M. (2021). Role of thyroid hormones in normal and abnormal central nervous system myelination in humans and rodents. Front Neuroendocrinol, 61, 100901. https://doi.org/10.1016/j.yfrne.2021.100901

Refetoff, S., Pappa, T., Williams, M. K., Matheus, M. G., Liao, X. H., Hansen, K., Nicol, L., Pierce, M., Blasco, P. A., Wiebers Jensen, M., Bernal, J., Weiss, R. E., Dumitrescu, A. M., & LaFranchi, S. (2021). Prenatal Treatment of Thyroid Hormone Cell Membrane Transport Defect Caused by MCT8 Gene Mutation. Thyroid, 31(5), 713-720. https://doi.org/10.1089/thy.2020.0306

Roth, S., Kinne, A., & Schweizer, U. (2010). The tricyclic antidepressant desipramine inhibits T3 import into primary neurons. Neurosci Lett, 478(1), 5-8. https://doi.org/10.1016/j.neulet.2010.04.055

Rozenblat, R., Tovin, A., Zada, D., Lebenthal-Loinger, I., Lerer-Goldshtein, T., & Appelbaum, L. (2022). Genetic and Neurological Deficiencies in the Visual System of mct8 Mutant Zebrafish. Int J Mol Sci, 23(5). https://doi.org/10.3390/ijms23052464

Salas-Lucia, F., Escamilla, S., Bianco, A. C., Dumitrescu, A., & Refetoff, S. (2024). Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome. JCI Insight, 9(7). https://doi.org/10.1172/jci.insight.174645

Salveridou, E., Mayerl, S., Sundaram, S. M., Markova, B., & Heuer, H. (2020). Tissue-Specific Function of Thyroid Hormone Transporters: New Insights from Mouse Models. Exp Clin Endocrinol Diabetes, 128(6-07), 423-427. https://doi.org/10.1055/a-1032-8328

Sandell, E., & Kolthoff, I. (1937). Micro determination of iodine by a catalytic method. Microchimica Acta, 1, 9-25.

Sardarova, N., Patel, T., Abugoukh, T., Kim, D., Yousuf, S., & Hammoude, M. (2025). Impact of Tyrosine Kinase Inhibitors on Thyroid Function in Chronic Myeloid Leukemia: A Systematic Review. Cureus. https://doi.org/10.7759/cureus.85196

Schwartz, C. E., May, M. M., Carpenter, N. J., Rogers, R. C., Martin, J., Bialer, M. G., Ward, J., Sanabria, J., Marsa, S., Lewis, J. A., Echeverri, R., Lubs, H. A., Voeller, K., Simensen, R. J., & Stevenson, R. E. (2005). Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. Am J Hum Genet, 77(1), 41-53. https://doi.org/10.1086/431313

Schweizer, U., Johannes, J., Bayer, D., & Braun, D. (2014). Structure and function of thyroid hormone plasma membrane transporters. Eur Thyroid J, 3(3), 143-153. https://doi.org/10.1159/000367858

Sharlin, D. S., Ng, L., Verrey, F., Visser, T. J., Liu, Y., Olszewski, R. T., Hoa, M., Heuer, H., & Forrest, D. (2018). Deafness and loss of cochlear hair cells in the absence of thyroid hormone transporters Slc16a2 (Mct8) and Slc16a10 (Mct10). Sci Rep, 8(1), 4403. https://doi.org/10.1038/s41598-018-22553-w

Silva, N., & Campinho, M. A. (2023). In a zebrafish biomedical model of human Allan-Herndon-Dudley syndrome impaired MTH signaling leads to decreased neural cell diversity. Front Endocrinol (Lausanne), 14, 1157685. https://doi.org/10.3389/fendo.2023.1157685

Sterner, Z. R., Jabrah, A., Shaidani, N. I., Horb, M. E., Dockery, R., Paul, B., & Buchholz, D. R. (2023). Development and metamorphosis in frogs deficient in the thyroid hormone transporter MCT8. Gen Comp Endocrinol, 331, 114179. https://doi.org/10.1016/j.ygcen.2022.114179

Szkudelska, K., & Nogowski, L. (2007). Genistein—A dietary compound inducing hormonal and metabolic changes. The Journal of Steroid Biochemistry and Molecular Biology, 105(1), 37-45. https://doi.org/https://doi.org/10.1016/j.jsbmb.2007.01.005

Thomas, J., Sairoz, Jose, A., Poojari, V. G., Shetty, S., K, S. P., Prabhu, R. V. K., & Rao, M. (2023). Role and Clinical Significance of Monocarboxylate Transporter 8 (MCT8) During Pregnancy. Reprod Sci, 30(6), 1758-1769. https://doi.org/10.1007/s43032-022-01162-z

Tonduti, D., Vanderver, A., Berardinelli, A., Schmidt, J. L., Collins, C. D., Novara, F., Genni, A. D., Mita, A., Triulzi, F., Brunstrom-Hernandez, J. E., Zuffardi, O., Balottin, U., & Orcesi, S. (2013). MCT8 deficiency: extrapyramidal symptoms and delayed myelination as prominent features. J Child Neurol, 28(6), 795-800. https://doi.org/10.1177/0883073812450944

Topliss, D. J., Kolliniatis, E., Barlow, J. W., Lim, C.-F., & Stockigt, J. R. (1989). Uptake of 3,5,3′-Triiodothyronine by Cultured Rat Hepatoma Cells Is Inhibitable by Nonbile Acid Cholephils, Diphenylhydantoin, and Nonsteroidal Antiinflammatory Drugs*. Endocrinology, 124(2), 980-986. https://doi.org/10.1210/endo-124-2-980

Trajkovic-Arsic, M., Muller, J., Darras, V. M., Groba, C., Lee, S., Weih, D., Bauer, K., Visser, T. J., & Heuer, H. (2010). Impact of monocarboxylate transporter-8 deficiency on the hypothalamus-pituitary-thyroid axis in mice. Endocrinology, 151(10), 5053-5062. https://doi.org/10.1210/en.2010-0593

Trajkovic, M., Visser, T. J., Mittag, J., Horn, S., Lukas, J., Darras, V. M., Raivich, G., Bauer, K., & Heuer, H. (2007). Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8. J Clin Invest, 117(3), 627-635. https://doi.org/10.1172/JCI28253

Valcarcel-Hernandez, V., Lopez-Espindola, D., Guillen-Yunta, M., Garcia-Aldea, A., Lopez de Toledo Soler, I., Barez-Lopez, S., & Guadano-Ferraz, A. (2022). Deficient thyroid hormone transport to the brain leads to impairments in axonal caliber and oligodendroglial development. Neurobiol Dis, 162, 105567. https://doi.org/10.1016/j.nbd.2021.105567

van Geest, F. S., Gunhanlar, N., Groeneweg, S., & Visser, W. E. (2021). Monocarboxylate Transporter 8 Deficiency: From Pathophysiological Understanding to Therapy Development. Front Endocrinol (Lausanne), 12, 723750. https://doi.org/10.3389/fendo.2021.723750

van Geest, F. S., Meima, M. E., Stuurman, K. E., Wolf, N. I., van der Knaap, M. S., Lorea, C. F., Poswar, F. O., Vairo, F., Brunetti-Pierri, N., Cappuccio, G., Bakhtiani, P., de Munnik, S. A., Peeters, R. P., Visser, W. E., & Groeneweg, S. (2020). Clinical and Functional Consequences of C-Terminal Variants in MCT8: A Case Series. The Journal of Clinical Endocrinology & Metabolism, 106(2), 539-553. https://doi.org/10.1210/clinem/dgaa795

Van Herck, S. L. J., Delbaere, J., Bourgeois, N. M. A., McAllan, B. M., Richardson, S. J., & Darras, V. M. (2015). Expression of thyroid hormone transporters and deiodinases at the brain barriers in the embryonic chicken: Insights into the regulation of thyroid hormone availability during neurodevelopment. General and Comparative Endocrinology, 214, 30-39. https://doi.org/https://doi.org/10.1016/j.ygcen.2015.02.021

Vancamp, P., & Darras, V. M. (2017). Dissecting the role of regulators of thyroid hormone availability in early brain development: Merits and potential of the chicken embryo model. Mol Cell Endocrinol, 459, 71-78. https://doi.org/10.1016/j.mce.2017.01.045

Vancamp, P., & Darras, V. M. (2018). From zebrafish to human: A comparative approach to elucidate the role of the thyroid hormone transporter MCT8 during brain development. Gen Comp Endocrinol, 265, 219-229. https://doi.org/10.1016/j.ygcen.2017.11.023

Vancamp, P., Deprez, M. A., Remmerie, M., & Darras, V. M. (2017). Deficiency of the Thyroid Hormone Transporter Monocarboxylate Transporter 8 in Neural Progenitors Impairs Cellular Processes Crucial for Early Corticogenesis. J Neurosci, 37(48), 11616-11631. https://doi.org/10.1523/JNEUROSCI.1917-17.2017

Vatine, G. D., Zada, D., Lerer-Goldshtein, T., Tovin, A., Malkinson, G., Yaniv, K., & Appelbaum, L. (2013). Zebrafish as a model for monocarboxyl transporter 8-deficiency. J Biol Chem, 288(1), 169-180. https://doi.org/10.1074/jbc.M112.413831

Visser, T. J. (2000). Cellular Uptake of Thyroid Hormones. In K. R. Feingold, S. F. Ahmed, B. Anawalt, M. R. Blackman, A. Boyce, G. Chrousos, E. Corpas, W. W. de Herder, K. Dhatariya, K. Dungan, J. Hofland, S. Kalra, G. Kaltsas, N. Kapoor, C. Koch, P. Kopp, M. Korbonits, C. S. Kovacs, W. Kuohung, B. Laferrère, M. Levy, E. A. McGee, R. McLachlan, R. Muzumdar, J. Purnell, R. Rey, R. Sahay, A. S. Shah, F. Singer, M. A. Sperling, C. A. Stratakis, D. L. Trence, & D. P. Wilson (Eds.), Endotext. MDText.com, Inc.

Copyright © 2000-2025, MDText.com, Inc.

Visser, W. E., Friesema, E. C., Jansen, J., & Visser, T. J. (2008). Thyroid hormone transport in and out of cells. Trends Endocrinol Metab, 19(2), 50-56. https://doi.org/10.1016/j.tem.2007.11.003

Visser, W. E., Friesema, E. C., & Visser, T. J. (2011). Minireview: thyroid hormone transporters: the knowns and the unknowns. Mol Endocrinol, 25(1), 1-14. https://doi.org/10.1210/me.2010-0095

Wagenaars, F., Cenijn, P., Scholze, M., Frädrich, C., Renko, K., Köhrle, J., & Hamers, T. (2024). Screening for endocrine disrupting chemicals inhibiting monocarboxylate 8 (MCT8) transporter facilitated thyroid hormone transport using a modified nonradioactive assay. Toxicology in Vitro, 96, 105770. https://doi.org/https://doi.org/10.1016/j.tiv.2023.105770

Wagenaars, F. M. A. (2025). Crossing the barrier: advancing endocrine disrupting chemical testing for thyroid hormone transport. Vrije Universiteit Amsterdam].

Walter, K. M., Miller, G. W., Chen, X., Harvey, D. J., Puschner, B., & Lein, P. J. (2019). Changes in thyroid hormone activity disrupt photomotor behavior of larval zebrafish. Neurotoxicology, 74, 47-57. https://doi.org/10.1016/j.neuro.2019.05.008

Wirth, E. K., Roth, S., Blechschmidt, C., Holter, S. M., Becker, L., Racz, I., Zimmer, A., Klopstock, T., Gailus-Durner, V., Fuchs, H., Wurst, W., Naumann, T., Brauer, A., de Angelis, M. H., Kohrle, J., Gruters, A., & Schweizer, U. (2009). Neuronal 3',3,5-triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome. J Neurosci, 29(30), 9439-9449. https://doi.org/10.1523/JNEUROSCI.6055-08.2009

Yadav, P., Sarode, L. P., Gaddam, R. R., Kumar, P., Bhatti, J. S., Khurana, A., & Navik, U. (2022). Zebrafish as an emerging tool for drug discovery and development for thyroid diseases. Fish Shellfish Immunol, 130, 53-60. https://doi.org/10.1016/j.fsi.2022.09.001

Zada, D., Blitz, E., & Appelbaum, L. (2017). Zebrafish - An emerging model to explore thyroid hormone transporters and psychomotor retardation. Mol Cell Endocrinol, 459, 53-58. https://doi.org/10.1016/j.mce.2017.03.004

Zada, D., Tovin, A., Lerer-Goldshtein, T., & Appelbaum, L. (2016). Pharmacological treatment and BBB-targeted genetic therapy for MCT8-dependent hypomyelination in zebrafish. Dis Model Mech, 9(11), 1339-1348. https://doi.org/10.1242/dmm.027227

Zada, D., Tovin, A., Lerer-Goldshtein, T., Vatine, G. D., & Appelbaum, L. (2014). Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation. PLoS Genet, 10(9), e1004615. https://doi.org/10.1371/journal.pgen.1004615