Horm Metab Res 2015; 47(12): 910-915
DOI: 10.1055/s-0035-1550008
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

MCT8 is Downregulated by Short Time Iodine Overload in the Thyroid Gland of Rats

E. C. L. de Souza*
1   Laboratory of Endocrine Physiology Doris Rosenthal, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
,
G. R. M. Dias*
1   Laboratory of Endocrine Physiology Doris Rosenthal, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
,
R. C. Cardoso
1   Laboratory of Endocrine Physiology Doris Rosenthal, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
,
L. P. Lima
1   Laboratory of Endocrine Physiology Doris Rosenthal, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
2   Departamento de Ciências Básicas, Pólo de Nova Friburgo, UFF, Brazil
,
R. S. Fortunato
1   Laboratory of Endocrine Physiology Doris Rosenthal, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
,
T. J. Visser
3   Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
,
M. Vaisman
4   Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
,
A. C. F. Ferreira
1   Laboratory of Endocrine Physiology Doris Rosenthal, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
5   Polo de Xerém/NUMPEX, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
,
D. P. Carvalho
1   Laboratory of Endocrine Physiology Doris Rosenthal, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
› Author Affiliations
Further Information

Publication History

received 07 January 2015

accepted 28 April 2015

Publication Date:
28 May 2015 (online)

Abstract

Wolff-Chaikoff effect is characterized by the blockade of thyroid hormone synthesis and secretion due to iodine overload. However, the regulation of monocarboxylate transporter 8 during Wolff-Chaikoff effect and its possible role in the rapid reduction of T4 secretion by the thyroid gland remains unclear. Patients with monocarboxylate transporter 8 gene loss-of-function mutations and monocarboxylate transporter 8 knockout mice were shown to have decreased serum T4 levels, indicating that monocarboxylate transporter 8 could be involved in the secretion of thyroid hormones from the thyroid gland. Herein, we aimed to evaluate the regulation of monocarboxylate transporter 8 during the Wolff-Chaikoff effect and the escape from iodine overload, besides the importance of iodine organification for this regulation. Monocarboxylate transporter 8 mRNA and protein levels significantly decreased after 1 day of NaI administration to rats, together with decreased serum T4; while no alteration was observed in LAT2 expression. Moreover, both monocarboxylate transporter 8 expression and serum T4 was restored after 6 days of NaI. The inhibition of thyroperoxidase activity by methimazole prevented the inhibitory effect of NaI on thyroid monocarboxylate transporter 8 expression, suggesting that an active thyroperoxidase is necessary for MCT8 downregulation by iodine overload, similarly to other thyroid markers, such as sodium iodide symporter. Therefore, we conclude that thyroid monocarboxylate transporter 8 expression is downregulated during iodine overload and that the normalization of its expression parallels the escape phenomenon. These data suggest a possible role for monocarboxylate transporter 8 in the changes of thyroid hormones secretion during the Wolff-Chaikoff effect and escape.

*  These authors contributed equally to this work.


Supporting Information

 
  • References

  • 1 Wolff J, Chaikoff IL. Plasma inorganic iodide as a homeostatic regulator of thyroid function. J Biol Chem 1948; 174: 555-564
  • 2 Wolff J, Chaikoff IL, Goldberg RC, Meier JR. The temporary nature of the inhibitory action of excess iodide on organic iodine synthesis in the normal thyroid. Endocrinology 1949; 45: 504-513
  • 3 Corvilain B, Van Sande J, Dumont JE. Inhibition by iodide of iodide binding to proteins: the “Wolff-Chaikoff” effect is caused by inhibition of H2O2 generation. Biochem Biophys Res Commun 1988; 154: 1287-1292
  • 4 Morand S, Chaaraoui M, Kaniewski J, Dème D, Ohayon R, Noel-Hudson MS, Virion A, Dupuy C. Effect of iodide on nicotinamide adenine dinucleotide phosphate oxidase activity and DUOX2 protein expression in isolated porcine thyroid follicles. Endocrinology 2003; 144: 1241-1248
  • 5 Cardoso LC, Martins DC, Figueiredo MD, Rosenthal D, Vaisman M, Violante AH, Carvalho DP. Ca(2 +)/nicotinamide adenine dinucleotide phosphate-dependent H(2)O(2) generation is inhibited by iodide in human thyroids. J Clin Endocrinol Metab 2001; 86: 4339-4343
  • 6 Van Sande J, Dumont JE. Effects of thyrotropin, prostlaglandin E1 and iodide on cyclic 3′,5′-AMP concentration in dog thyroid slices. Biochim Biophys Acta 1973; 313: 320-328
  • 7 Van Sande J, Grenier G, Willens C, Dumont JE. Inhibition by iodide of the activation of the thyroid cyclic 3′,5′-AMP system. Endocrinology 1975; 96: 781-786
  • 8 Van Sande J, Cochaux P, Dumont JE. Further characterization of the iodide inhibitory effect on the cyclic AMP system in dog thyroid slices. Mol Cell Endocrinol 1985; 40: 181-192
  • 9 Cochaux P, Van Sande J, Swillens S, Dumont JE. Iodide-induced inhibition of adenylate cyclase activity in horse and dog thyroid. Eur J Biochem 1987; 170: 435-442
  • 10 Eng PHK, Cardona GR, Ang SLF, Previti M, Alex S, Carrasco N, Chin WW, Braverman LE. Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. Endocrinology 1999; 140: 3404-3410
  • 11 Ferreira ACF, Lima LP, Araújo RL, Müller G, Rocha RP, Rosenthal D, Carvalho DP. Rapid regulation of thyroid sodium–iodide symporter activity by thyrotrophin and iodine. J Endocrinol 2005; 184: 69-76
  • 12 Calil-Silveira J, Serrano-Nascimento C, Nunes MT. Iodide treatment acutely increases pendrin (SLC26A4) mRNA expression in the rat thyroid and the PCCl3 thyroid cell line by transcriptional mechanisms. Mol Cell Endocrinol 2012; 350: 118-124
  • 13 Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ. Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem 2003; 278: 40128-40135
  • 14 Lafreniere RG, Carrel L, Willard HF. A novel transmembrane transporter encoded by XPCT gene in Xq13.2. Human Mol Genet 1994; 3: 1133-1139
  • 15 Friesema EC, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barret TG, Mancilla EE, Svensson J, Kester MH, Kuiper GG, Balkassmi S, Uitterlinden AG, Koehrle J, Rodien P, Halestrap AP, Visser TJ. Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet 2004; 364: 1435-1437
  • 16 Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S. A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am J Human Genet 2004; 74: 168-175
  • 17 Trajkovic-Arsic M, Muller J, Darras VM, Groba C, Lee S, Weih D, Bauer K, Visser TJ, Heuer H. Impact of Monocarboxylate Transporter-8 Deficiency on the Hypothalamus-Pituitary-Thyroid Axis in Mice. Endocrinology 2010; 151: 5053-5062
  • 18 Di Cosmo C, Liao X-H, Dumitrescu AM, Philp NJ, Weiss RE, Refetoff S. Mice deficient in MCT8 reveal a mechanism regulating thyroid hormone secretion. J Clin Invest 2010; 120: 3377-3388
  • 19 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C (T)) method. Methods 2001; 25: 402-408
  • 20 Mustafa S, Elgazzar A. Influence of Chronic Exposure to Cold Environment on Thyroid Gland Function in Rabbits. Horm Metab Res 2014; 46: 546-549
  • 21 Uyttersprot N, Pelgrims N, Carrasco N, Gervy C, Maenhaut C, Dumont JE, Miot F. Moderate doses of iodide in vivo inhibit cell proliferation and the expression of thyroperoxidase and Na+/I– symporter mRNAs in dog thyroid. Mol Cell Endocrinol 1997; 131: 195-203
  • 22 Wirth EK, Chiu-Ugalde J, Sapin R, Klein MO, Mossbrugger I, Quintanilha-Martinez L, de Angelis MH, Krude H, Riebel T, Rothe K, Kohrle J, Schmid KW, Schweizer U, Gruters A. Monocarboxylate transporter 8 deficiency: altered thyroid morphology and persistent high triiodothyronine/thyroxine ratio after thyroidectomy. Eur J Endocrinol 2011; 165: 555-561
  • 23 Ritchie JW, Peter GJ, Shi YB, Taylor PM. Thyroid hormone transport by 4F2hc-IU12 heterodimers expressed in Xenopus oocytes. J Endocrinol 1999; 163: R5-R9
  • 24 Friesema EC, Docter R, Moerings EP, Verrey F, Krenning EP, Hennemann G, Visser TJ. Thyroid hormone transport by the heterodimeric human system L amino acid transporter. Endocrinology 2001; 142: 4339-4348
  • 25 Braun D, Wirth EK, Schweizer U. Thyroid hormone transporters in the brain. Reviews in the Neuroscience 2010; 21: 173-186
  • 26 Wirth EK, Roth S, Blechschmidt C, Holter SM, Becker L, Racz I, Zimmer A, Klopstock T, Gailus-Durner V, Fuchs H, Wurst W, Naumann T, Brauer A, de Angelis MH, Kohrle J, Gruters A, Schweizer U. 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 2009; 29: 9439-9449
  • 27 Braum D, Wirt EK, Wohlgemuth F, Reix N, Klein MO, Gruters A, Kohrle J, Schweizer U. Aminoaciduria, but normal thyroid hormone levels and signaling, in mice lacking the amino acid and thyroid hormone transporter SLC7A8. Biochem J 2011; 439: 249-255
  • 28 Heuer H, Visser TJ. The pathophysiological consequences of thyroid hormone transporter deficiencies: Insights from mouse models. Biochim Biophys Acta 2013; 1830: 3974-3978
  • 29 Cazarin JM, Andrade BM, Carvalho DP. AMP-Activated Protein Kinase Activation Leads to Lysome-Mediated Na + /I-Symporter Protein Degradation in Rat Thyroid Cells. Horm Metab Res 2014; 46: 313-317
  • 30 Twyffels L, Strickaert A, Virreira M, Massart C, Van Sande J, Wauquier C, Beauwens R, Dumont JE, Galietta LJ, Boom A, Kruys V. Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte. Am J Physiol Cell Physiol 2014; 307: C1102-C1112
  • 31 Thomasz L, Oglio R, Toro Rivandeira D, Dagrosa MA, Jahn G, Piganataro OP, Sartorio G, Pisareva MA, Juvenal GJ. Inhibition of goiter growth and of cyclic AMP formation in rat thyroid by 2-iodohexadecanal. Mol Cell Endocrinol 2010; 317: 141-147
  • 32 Thomasz L, Oglio R, Dagrosa MA, Leon K, Pisarev MA, Juvenal GJ. 6 Iodo-_-lactone reproduces many but not all the effects of iodide. Mol Cell Endocrinol 2010; 323: 161-166