Skip to main content
SpringerLink
Log in

Deficit in Thyroid Hormone Transporters and Brain Development

  • Chapter
  • First Online:
Thyroid Hormone Disruption and Neurodevelopment

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

  • 773 Accesses

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Abbreviations

BBB:

Blood–brain barrier

CSF:

Cerebrospinal fluid

MCT:

Monocarboxylate transporter

ntcp:

Na+/taurocholate cotransporting polypeptide

oatp:

Organic anion transporting polypeptide

T4, thyroxine:

T3, 3,3′, 5-triiodo-l-thyronine

References

  • Abe T, Kakyo M, Sakagami H, Tokui T, Nishio T, Tanemoto M et al (1998) Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2. J Biol Chem 273(35):22395–22401

    Article  CAS  PubMed  Google Scholar 

  • Abe T, Kakyo M, Tokui T, Nakagomi R, Nishio T, Nakai D et al (1999) Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J Biol Chem 274(24):17159–17163

    Article  CAS  PubMed  Google Scholar 

  • Abe T, Unno M, Onogawa T, Tokui T, Kondo TN, Nakagomi R et al (2001) LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology 120(7):1689–1699

    Article  CAS  PubMed  Google Scholar 

  • Abe T, Suzuki T, Unno M, Tokui T, Ito S (2002) Thyroid hormone transporters: recent advances. Trends Endocrinol Metab 13(5):215–220

    Article  CAS  PubMed  Google Scholar 

  • Albert A, Keating FR Jr (1952) The role of the gastrointestinal tract, including the liver, in the metabolism of radiothyroxine. Endocrinology 51(5):427–443

    Article  CAS  PubMed  Google Scholar 

  • Alkemade A, Friesema EC, Unmehopa UA, Fabriek BO, Kuiper GG, Leonard JL et al (2005) Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus. J Clin Endocrinol Metab 90(7):4322–4334

    Article  CAS  PubMed  Google Scholar 

  • Alkemade A, Friesema EC, Kuiper GG, Wiersinga WM, Swaab DF, Visser TJ et al (2006) Novel neuroanatomical pathways for thyroid hormone action in the human anterior pituitary. Eur J Endocrinol 154(3):491–500

    Article  CAS  PubMed  Google Scholar 

  • Angeletti RH, Novikoff PM, Juvvadi SR, Fritschy JM, Meier PJ, Wolkoff AW (1997) The choroid plexus epithelium is the site of the organic anion transport protein in the brain. Proc Natl Acad Sci U S A 94(1):283–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balazs R, Brooksbank BW, Davison AN, Eayrs JT, Wilson DA (1969) The effect of neonatal thyroidectomy on myelination in the rat brain. Brain Res 15(1):219–232

    Article  CAS  PubMed  Google Scholar 

  • Balazs R, Kovacs S, Cocks WA, Johnson AL, Eayrs JT (1971) Effect of thyroid hormone on the biochemical maturation of rat brain: postnatal cell formation. Brain Res 25(3):555–570

    Article  CAS  PubMed  Google Scholar 

  • Bernal J, Guadano-Ferraz A, Morte B (2015) Thyroid hormone transporters—functions and clinical implications. Nat Rev Endocrinol 11(7):406–417

    Article  CAS  PubMed  Google Scholar 

  • Beslin A, Chantoux F, Blondeau JP, Francon J (1995) Relationship between the thyroid hormone transport system and the Na(+)-H+ exchanger in cultured rat brain astrocytes. Endocrinology 136(12):5385–5390

    Article  CAS  PubMed  Google Scholar 

  • Blondeau JP, Osty J, Francon J (1988) Characterization of the thyroid hormone transport system of isolated hepatocytes. J Biol Chem 263(6):2685–2692

    Article  CAS  PubMed  Google Scholar 

  • Blondeau JP, Beslin A, Chantoux F, Francon J (1993) Triiodothyronine is a high-affinity inhibitor of amino acid transport system L1 in cultured astrocytes. J Neurochem 60(4):1407–1413

    Article  CAS  PubMed  Google Scholar 

  • Bronger H, Konig J, Kopplow K, Steiner HH, Ahmadi R, Herold-Mende C et al (2005) ABCC drug efflux pumps and organic anion uptake transporters in human gliomas and the blood-tumor barrier. Cancer Res 65(24):11419–11428

    Article  CAS  PubMed  Google Scholar 

  • Cavallaro T, Martone RL, Dwork AJ, Schon EA, Herbert J (1990) The retinal pigment epithelium is the unique site of transthyretin synthesis in the rat eye. Invest Ophthalmol Vis Sci 31(3):497–501

    CAS  PubMed  Google Scholar 

  • Centanni M, Robbins J (1987) Role of sodium in thyroid hormone uptake by rat skeletal muscle. J Clin Invest 80(4):1068–1072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chanoine JP, Alex S, Fang SL, Stone S, Leonard JL, Korhle J et al (1992) Role of transthyretin in the transport of thyroxine from the blood to the choroid plexus, the cerebrospinal fluid, and the brain. Endocrinology 130(2):933–938

    CAS  PubMed  Google Scholar 

  • Chantoux F, Blondeau JP, Francon J (1995) Characterization of the thyroid hormone transport system of cerebrocortical rat neurons in primary culture. J Neurochem 65(6):2549–2554

    Article  CAS  PubMed  Google Scholar 

  • Chatonnet F, Flamant F, Morte B (2015) A temporary compendium of thyroid hormone target genes in brain. Biochim Biophys Acta 1849(2):122–129

    Article  CAS  PubMed  Google Scholar 

  • DiStefano JJ III, Nguyen TT, Yen YM (1992) Sites and patterns of absorption of 3,5,3′-triiodothyronine and thyroxine along rat small and large intestines. Endocrinology 131(1):275–280

    Article  CAS  PubMed  Google Scholar 

  • Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S (2004) A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am J Hum Genet 74(1):168–175

    Article  CAS  PubMed  Google Scholar 

  • Dumitrescu AM, Liao XH, Weiss RE, Millen K, Refetoff S (2006) Tissue-specific thyroid hormone deprivation and excess in monocarboxylate transporter (mct) 8-deficient mice. Endocrinology 147(9):4036–4043

    Article  CAS  PubMed  Google Scholar 

  • Eayrs JT (1960) Influence of the thyroid on the central nervous system. Br Med Bull 16:122–127

    Article  CAS  PubMed  Google Scholar 

  • Francon J, Chantoux F, Blondeau JP (1989) Carrier-mediated transport of thyroid hormones into rat glial cells in primary culture. J Neurochem 53(5):1456–1463

    Article  CAS  PubMed  Google Scholar 

  • Friesema EC, Docter R, Moerings EP, Stieger B, Hagenbuch B, Meier PJ et al (1999) Identification of thyroid hormone transporters. Biochem Biophys Res Commun 254(2):497–501

    Article  CAS  PubMed  Google Scholar 

  • Friesema EC, Docter R, Moerings EP, Verrey F, Krenning EP, Hennemann G et al (2001) Thyroid hormone transport by the heterodimeric human system L amino acid transporter. Endocrinology 142(10):4339–4348

    Article  CAS  PubMed  Google Scholar 

  • Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ (2003) Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem 278(41):40128–40135

    Article  CAS  PubMed  Google Scholar 

  • Friesema EC, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M et al (2004) Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet 364(9443):1435–1437

    Article  CAS  PubMed  Google Scholar 

  • Friesema EC, Jansen J, Visser TJ (2005) Thyroid hormone transporters. Biochem Soc Trans 33(Pt 1):228–232

    Article  CAS  PubMed  Google Scholar 

  • Friesema EC, Kuiper GG, Jansen J, Visser TJ, Kester MH (2006a) Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism. Mol Endocrinol 20(11):2761–2772

    Article  CAS  PubMed  Google Scholar 

  • Friesema EC, Jansen J, Heuer H, Trajkovic M, Bauer K, Visser TJ (2006b) Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8. Nat Clin Pract Endocrinol Metab 2(9):512–523

    Article  CAS  PubMed  Google Scholar 

  • Fujiwara K, Adachi H, Nishio T, Unno M, Tokui T, Okabe M et al (2001) Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology 142(5):2005–2012

    Article  CAS  PubMed  Google Scholar 

  • Galton VA, St Germain DL, Whittemore S (1986) Cellular uptake of 3,5,3′-triiodothyronine and thyroxine by red blood and thymus cells. Endocrinology 118(5):1918–1923

    Article  CAS  PubMed  Google Scholar 

  • Gao B, Stieger B, Noe B, Fritschy JM, Meier PJ (1999) Localization of the organic anion transporting polypeptide 2 (Oatp2) in capillary endothelium and choroid plexus epithelium of rat brain. J Histochem Cytochem 47(10):1255–1264

    Article  CAS  PubMed  Google Scholar 

  • Gingrich SA, Smith PJ, Shapiro LE, Surks MI (1985) 5,5'-Diphenylhydantoin (phenytoin) attenuates the action of 3,5,3′-triiodo-L-thyronine in cultured GC cells. Endocrinology 116(6):2306–2313

    Article  CAS  PubMed  Google Scholar 

  • Guadano-Ferraz A, Obregon MJ, St Germain DL, Bernal J (1997) The type 2 iodothyronine deiodinase is expressed primarily in glial cells in the neonatal rat brain. Proc Natl Acad Sci U S A 94(19):10391–10396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hagenbuch B, Dawson P (2004) The sodium bile salt cotransport family SLC10. Pflugers Arch 447(5):566–570

    Article  CAS  PubMed  Google Scholar 

  • Hagenbuch B, Stieger B, Foguet M, Lubbert H, Meier PJ (1991) Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc Natl Acad Sci U S A 88(23):10629–10633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halestrap AP (2013) The SLC16 gene family—structure, role and regulation in health and disease. Mol Aspects Med 34(2–3):337–349

    Article  CAS  PubMed  Google Scholar 

  • Haynes BF, Hemler ME, Mann DL, Eisenbarth GS, Shelhamer J, Mostowski HS et al (1981) Characterization of a monoclonal antibody (4F2) that binds to human monocytes and to a subset of activated lymphocytes. J Immunol 126(4):1409–1414

    Article  CAS  PubMed  Google Scholar 

  • Hennemann G, Docter R, Friesema EC, de Jong M, Krenning EP, Visser TJ (2001) Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability. Endocr Rev 22(4):451–476

    Article  CAS  PubMed  Google Scholar 

  • Heuer H, Maier MK, Iden S, Mittag J, Friesema EC, Visser TJ et al (2005) The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations. Endocrinology 146(4):1701–1706

    Article  CAS  PubMed  Google Scholar 

  • Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP et al (1999) A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem 274(52):37161–37168

    Article  CAS  PubMed  Google Scholar 

  • Ito A, Yamaguchi K, Onogawa T, Unno M, Suzuki T, Nishio T et al (2002) Distribution of organic anion-transporting polypeptide 2 (oatp2) and oatp3 in the rat retina. Invest Ophthalmol Vis Sci 43(3):858–863

    PubMed  Google Scholar 

  • Jacquemin E, Hagenbuch B, Stieger B, Wolkoff AW, Meier PJ (1994) Expression cloning of a rat liver Na(+)-independent organic anion transporter. Proc Natl Acad Sci U S A 91(1):133–137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jansen J, Friesema EC, Milici C, Visser TJ (2005) Thyroid hormone transporters in health and disease. Thyroid 15(8):757–768

    Article  CAS  PubMed  Google Scholar 

  • Konig J, Cui Y, Nies AT, Keppler D (2000a) A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane. Am J Physiol Gastrointest Liver Physiol 278(1):G156–G164

    Article  CAS  PubMed  Google Scholar 

  • Konig J, Cui Y, Nies AT, Keppler D (2000b) Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide. J Biol Chem 275(30):23161–23168

    Article  CAS  PubMed  Google Scholar 

  • Krenning E, Docter R, Bernard B, Visser T, Hennemann G (1981) Characteristics of active transport of thyroid hormone into rat hepatocytes. Biochim Biophys Acta 676(3):314–320

    Article  CAS  PubMed  Google Scholar 

  • Kusuhara H, He Z, Nagata Y, Nozaki Y, Ito T, Masuda H et al (2003) Expression and functional involvement of organic anion transporting polypeptide subtype 3 (Slc21a7) in rat choroid plexus. Pharm Res 20(5):720–727

    Article  CAS  PubMed  Google Scholar 

  • Lee WS, Berry MJ, Hediger MA, Larsen PR (1993) The type I iodothyronine 5′-deiodinase messenger ribonucleic acid is localized to the S3 segment of the rat kidney proximal tubule. Endocrinology 132(5):2136–2140

    Article  CAS  PubMed  Google Scholar 

  • Malandro MS, Kilberg MS (1996) Molecular biology of mammalian amino acid transporters. Annu Rev Biochem 65:305–336

    Article  CAS  PubMed  Google Scholar 

  • Mastroberardino L, Spindler B, Pfeiffer R, Skelly PJ, Loffing J, Shoemaker CB et al (1998) Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family. Nature 395(6699):288–291

    Article  CAS  PubMed  Google Scholar 

  • Mayerl S, Visser TJ, Darras VM, Horn S, Heuer H (2012) Impact of Oatp1c1 deficiency on thyroid hormone metabolism and action in the mouse brain. Endocrinology 153(3):1528–1537

    Article  CAS  PubMed  Google Scholar 

  • Mayerl S, Muller J, Bauer R, Richert S, Kassmann CM, Darras VM et al (2014) Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. J Clin Invest 124(5):1987–1999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meier PJ, Stieger B (2002) Bile salt transporters. Annu Rev Physiol 64:635–661

    Article  CAS  PubMed  Google Scholar 

  • Ohtsuki S, Takizawa T, Takanaga H, Terasaki N, Kitazawa T, Sasaki M et al (2003) In vitro study of the functional expression of organic anion transporting polypeptide 3 at rat choroid plexus epithelial cells and its involvement in the cerebrospinal fluid-to-blood transport of estrone-3-sulfate. Mol Pharmacol 63(3):532–537

    Article  CAS  PubMed  Google Scholar 

  • Ohtsuki S, Takizawa T, Takanaga H, Hori S, Hosoya K, Terasaki T (2004) Localization of organic anion transporting polypeptide 3 (oatp3) in mouse brain parenchymal and capillary endothelial cells. J Neurochem 90(3):743–749

    Article  CAS  PubMed  Google Scholar 

  • Oppenheimer JH, Schwartz HL (1997) Molecular basis of thyroid hormone-dependent brain development. Endocr Rev 18(4):462–475

    CAS  PubMed  Google Scholar 

  • Osty J, Jego L, Francon J, Blondeau JP (1988) Characterization of triiodothyronine transport and accumulation in rat erythrocytes. Endocrinology 123(5):2303–2311

    Article  CAS  PubMed  Google Scholar 

  • Palha JA, Fernandes R, de Escobar GM, Episkopou V, Gottesman M, Saraiva MJ (2000) Transthyretin regulates thyroid hormone levels in the choroid plexus, but not in the brain parenchyma: study in a transthyretin-null mouse model. Endocrinology 141(9):3267–3272

    Article  CAS  PubMed  Google Scholar 

  • Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ (2002) Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol 16(10):2283–2296

    Article  CAS  PubMed  Google Scholar 

  • Porterfield SP, Hendrich CE (1993) The role of thyroid hormones in prenatal and neonatal neurological development—current perspectives. Endocr Rev 14(1):94–106

    CAS  PubMed  Google Scholar 

  • Refetoff S, Weiss RE, Usala SJ (1993) The syndromes of resistance to thyroid hormone. Endocr Rev 14(3):348–399

    CAS  PubMed  Google Scholar 

  • Roberts LM, Woodford K, Zhou M, Black DS, Haggerty JE, Tate EH et al (2008) Expression of the thyroid hormone transporters monocarboxylate transporter-8 (SLC16A2) and organic ion transporter-14 (SLCO1C1) at the blood-brain barrier. Endocrinology 149(12):6251–6261

    Article  CAS  PubMed  Google Scholar 

  • Schwartz CE, May MM, Carpenter NJ, Rogers RC, Martin J, Bialer MG et al (2005) Allan-Herndon-Dudley syndrome and the MCT8 thyroid hormone transporter. Am J Hum Genet. 77(1):41–53

    Google Scholar 

  • Southwell BR, Duan W, Alcorn D, Brack C, Richardson SJ, Kohrle J et al (1993) Thyroxine transport to the brain: role of protein synthesis by the choroid plexus. Endocrinology 133(5):2116–2126

    Article  CAS  PubMed  Google Scholar 

  • Sugiyama D, Kusuhara H, Taniguchi H, Ishikawa S, Nozaki Y, Aburatani H et al (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(44):43489–43495

    Article  CAS  PubMed  Google Scholar 

  • Suzuki T, Onogawa T, Asano N, Mizutamari H, Mikkaichi T, Tanemoto M et al (2003) Identification and characterization of novel rat and human gonad-specific organic anion transporters. Mol Endocrinol 17(7):1203–1215

    Article  CAS  PubMed  Google Scholar 

  • Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M et al (2000) Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun 273(1):251–260

    Article  CAS  PubMed  Google Scholar 

  • Thompson CC, Potter GB (2000) Thyroid hormone action in neural development. Cereb Cortex 10(10):939–945

    Article  CAS  PubMed  Google Scholar 

  • Tohyama K, Kusuhara H, Sugiyama Y (2004) Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the transport of thyroxine across the blood-brain barrier. Endocrinology 145(9):4384–4391

    Article  CAS  PubMed  Google Scholar 

  • Topliss DJ, Kolliniatis E, Barlow JW, Lim CF, Stockigt JR (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

    Article  CAS  PubMed  Google Scholar 

  • Toyohara T, Suzuki T, Morimoto R, Akiyama Y, Souma T, Shiwaku HO et al (2009) SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation. J Am Soc Nephrol 20(12):2546–2555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trajkovic M, Visser TJ, Mittag J, Horn S, Lukas J, Darras VM et al (2007) Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8. J Clin Invest 117(3):627–635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wells RG, Lee WS, Kanai Y, Leiden JM, Hediger MA (1992) The 4F2 antigen heavy chain induces uptake of neutral and dibasic amino acids in Xenopus oocytes. J Biol Chem 267(22):15285–15288

    Article  CAS  PubMed  Google Scholar 

  • Yen PM (2001) Physiological and molecular basis of thyroid hormone action. Physiol Rev 81(3):1097–1142

    Article  CAS  PubMed  Google Scholar 

  • Yen PM (2003) Molecular basis of resistance to thyroid hormone. Trends Endocrinol Metab 14(7):327–333

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Takehiro Suzuki & Takaaki Abe

  2. Department of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, Miyagi, Japan

    Takehiro Suzuki & Takaaki Abe

  3. Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Takaaki Abe

Authors
  1. Takehiro Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takaaki Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takaaki Abe .

Editor information

Editors and Affiliations

  1. Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Noriyuki Koibuchi

  2. Laboratory of Hormonal Regulation Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore, Singapore

    Paul M. Yen

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this chapter

Cite this chapter

Suzuki, T., Abe, T. (2016). Deficit in Thyroid Hormone Transporters and Brain Development. In: Koibuchi, N., Yen, P.M. (eds) Thyroid Hormone Disruption and Neurodevelopment. Contemporary Clinical Neuroscience. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3737-0_11

Download citation

Publish with us

Policies and ethics

Search

Navigation