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Nuklearmedizin 2015; 54(03): 77-81
DOI: 10.1055/s-0037-1616606
Innovation Schilddrü se
Schattauer GmbH

Die Bedeutung von Schilddrü senhormontransportern

The importance of thyroid hormone transporters
D. Braun
1   Institut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms Universität Bonn
› Author Affiliations
Further Information

Publication History

received: 19 August 2014

accepted: 20 May 2015

Publication Date:
11 January 2018 (online)

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Zusammenfassung

William Allan, Nash Herndon und Florence Dudley publizierten 1944 Beobachtungen zu einem vererbbaren Syndrom, das sich durch Muskelschwä che, mentale Retardierung (Intelligenzquotient < 30) und Entwicklungsverzö gerungen auszeichnete. Die mä nnlichen Patienten waren unfä hig, ihren Kopf zu halten, hatten Sprachdefizite und konnten meist weder sitzen noch gehen. Inzwischen ist bekannt, dass das Allan-Herndon-Dudley- Syndrom (AHDS) nach dem fragilen X-Syndrom die zweite beschriebene X-chromosomal vererbte Krankheit ist.

Als diagnostisches Kriterium ist inzwischen eine bestimmte Schilddrü senhormonkonstellation hinzugekommen. Die Krankheit ist mit Mutationen im X-chromosomal lokalisierten SLC16A2 Gens assoziiert. SLC16A2 kodiert für einen spezifischen Plasmamembran- Schilddrü senhormon-Transporter, den Monocarboxylattransporter 8 (MCT8)

Summary

Symptoms of a newly discovered X-chromosomal severe mental retardation disease were published by William Allan, Nash Herndon and Florence Dudley in 1944. Patients suffered from muscle weakness and a developmental delay not able to sit, walk and speak. In addition, they showed an endocrinological phenotype with abnormal thyroid hormone constellations.

The reason for the Allan-Herndon-Dudley syndrome was found in a mutation of the monocarboxylate transporter 8 (MCT8, SLC16A2), a specific thyroid hormone transporter.

Schlüsselwörter

Allan-Herndon-Dudley-Syndrom

Keywords

Allan-Herndon-Dudley syndrome
 

  • Literatur

  • 1 Bagamasbad P, Denver RJ. Mechanisms and significance of nuclear receptor auto- and cross-regulation. Gen Comp Endocrinol 2011; 170: 3-17.
    CrossrefPubMedGoogle Scholar
  • 2 Bernal J. Thyroid hormone resistance syndromes. Endocrinol Nutr 2011; 58: 185-196.
    CrossrefPubMedGoogle Scholar
  • 3 Bianco AC, Salvatore D, Gereben B. et al. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 2002; 23: 38-89.
    CrossrefPubMedGoogle Scholar
  • 4 Biebermann H, Ambrugger P, Tarnow P. et al. 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 2005; 153: 359-366.
    CrossrefPubMedGoogle Scholar
  • 5 Braun D, Wirth EK, Wohlgemuth F. et al. Aminoaciduria, but normal thyroid hormone levels and signalling, in mice lacking the amino acid and thyroid hormone transporter Slc7a8. Biochem J 2011; 439: 249-255.
    CrossrefPubMedGoogle Scholar
  • 6 Del Amo EM, Urtti A, Yliperttula M. Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2. Eur J Pharm Sci 2008; 35: 161-174.
    CrossrefPubMedGoogle Scholar
  • 7 Di Cosmo C, Liao XH, Dumitrescu AM. et al. Mice deficient in MCT8 reveal a mechanism regulating thyroid hormone secretion. J Clin Invest 2010; 120: 3377-3388.
    CrossrefPubMedGoogle Scholar
  • 8 Dumitrescu AM, Liao XH, Best TB. et al. A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am J Hum Genet 2004; 74: 168-175.
    CrossrefPubMedGoogle Scholar
  • 9 Friesema EC, Ganguly S, Abdalla A. et al. Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem 2003; 278: 40128-40135.
    PubMedGoogle Scholar
  • 10 Friesema EC, Grueters A, Biebermann H. et al. Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet 2004; 364: 1435-1437.
    CrossrefPubMedGoogle Scholar
  • 11 Friesema EC, Jansen J, Jachtenberg JW. et al. Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10. Mol Endocrinol 2008; 22: 1357-1369.
    CrossrefPubMedGoogle Scholar
  • 12 Frints SG, Lenzner S, Bauters M. et al. MCT8 mutation analysis and identification of the first female with Allan-Herndon-Dudley syndrome due to loss of MCT8 expression. Eur J Hum Genet 2008; 16: 1029-1037.
    CrossrefPubMedGoogle Scholar
  • 13 Fu J, Dumitrescu AM. Inherited defects in thyroid hormone cell-membrane transport and metabolism. Best Pract Res Clin Endocrinol Metab 2014; 28: 189-201.
    CrossrefPubMedGoogle Scholar
  • 14 Hagenbuch B. Cellular entry of thyroid hormones by organic anion transporting polypeptides. Best Pract Res Clin Endocrinol Metab 2007; 21: 209-221.
    CrossrefPubMedGoogle Scholar
  • 15 Halestrap AP, Meredith D. The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 2004; 447: 619-628.
    CrossrefPubMedGoogle Scholar
  • 16 Hennemann G, Docter R, Friesema EC. et al. J. Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability. Endocr Rev 2001; 22: 451-476.
    CrossrefPubMedGoogle Scholar
  • 17 Holden KR, Zuniga OF, May MM. et al. X-linked MCT8 gene mutations: characterization of the pediatric neurologic phenotype. J Child Neurol 2005; 20: 852-857.
    CrossrefPubMedGoogle Scholar
  • 18 Mebis L, van den Berghe G. The hypothalamus-pituitary-thyroid axis in critical illness. Neth J Med 2009; 67: 332-340.
    PubMedGoogle Scholar
  • 19 Patel J, Landers K, Li H. et al. Thyroid hormones and fetal neurological development. J Endocrinol 2011; 209: 1-8.
    CrossrefPubMedGoogle Scholar
  • 20 Schwartz CE, May MM, Carpenter NJ. et al. Allan Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. Am J Hum Genet 2005; 77: 41-53.
    CrossrefPubMedGoogle Scholar
  • 21 Schwartz CE, Stevenson RE. The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome. Best Pract Res Clin Endocrinol Metab 2007; 21: 307-321.
    CrossrefPubMedGoogle Scholar
  • 22 Schweizer U, Kohrle J. Function of thyroid hormone transporters in the central nervous system. Biochim Biophys Acta 2013; 1830: 3965-3973.
    CrossrefPubMedGoogle Scholar
  • 23 Song Y, Yao X, Ying H. Thyroid hormone action in metabolic regulation. Protein Cell 2011; 2: 358-368.
    CrossrefPubMedGoogle Scholar
  • 24 Tonjes A, Karger S, Koch CA. et al. Impaired enteral levothyroxine absorption in hypothyroidism refractory to oral therapy after thyroid ablation for papillary thyroid cancer: case report and kinetic studies. Thyroid 2006; 16: 1047-1051.
    CrossrefPubMedGoogle Scholar
  • 25 Verge CF, Konrad D, Cohen M. et al. Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency. J Clin Endocrinol Metab 2012; 97: 4515-4523.
    CrossrefPubMedGoogle Scholar
  • 26 Wemeau JL, Pigeyre M, Proust-Lemoine E. et al. Beneficial effects of propylthiouracil plus L-thyroxine treatment in a patient with a mutation in MCT8. J Clin Endocrinol Metab 2008; 93: 2084-2088.
    CrossrefPubMedGoogle Scholar
  • 27 Williams GR, Bassett JH. Deiodinases: the balance of thyroid hormone: local control of thyroid hormone action: role of type 2 deiodinase. J Endocrinol 2011; 209: 261-272.
    CrossrefPubMedGoogle Scholar
  • 28 Wirth EK, Sheu SY, Chiu-Ugalde J. et al. Monocarboxylate transporter 8 deficiency: altered thyroid morphology and persistent high triiodothyronine/thyroxine ratio after thyroidectomy. Eur J Endocrinol 2011; 165: 555-561.
    CrossrefPubMedGoogle Scholar