Skip to main content
Top
Published in: Thyroid Research 1/2010

Open Access 01-12-2010 | Research

Effect of thyroid statuses on sodium/iodide symporter (NIS) gene expression in the extrathyroidal tissues in mice

Authors: Md Harun-Or-Rashid, Masato Asai, Xiao-yang Sun, Yoshitaka Hayashi, Junichi Sakamoto, Yoshiharu Murata

Published in: Thyroid Research | Issue 1/2010

Login to get access

Abstract

Background

Iodide that is essential for thyroid hormone synthesis is actively transported into the thyroid follicular cells via sodium/iodide symporter (NIS) protein in vertebrates. It is well known that NIS expression in thyroid is regulated by the thyroid statuses mainly through thyroid stimulating hormone (TSH). Although NIS mRNA expressions in extrathyroidal tissues have been qualitatively reported, their regulation by thyroid statuses has not been well clarified.

Methods

Male ICR mice aged four weeks were assigned into three groups (control, hypothyroid, and hyperthyroid). Hypothyroid group of mice were treated with 0.02% methimazole in drinking water and hyperthyroid group of mice received intraperitoneal injection (4 μg L-T4 twice a week) for four weeks. NIS mRNA expression levels in the tissues were evaluated using Northern blot hybridization and quantitative real-time RTPCR (qPCR). Additionally, end-point RTPCR for the thyroid follicular cell-characteristic genes (TSH receptor, TSHR; thyroid transcription factor-1, TTF1; and paired box gene 8, Pax8) was carried out.

Results

By Northern blot analysis, NIS mRNA was detected in thyroid and stomach. In addition to these organs, qPCR revealed the expression also in the submandibular gland, colon, testis, and lung. Expression of NIS mRNA in thyroid was significantly increased in hypothyroid and decreased in hyperthyroid group. Trends of NIS mRNA expression in extrathyroidal tissues were not in line with that in the thyroid gland in different thyroid statuses. Only in lung, NIS mRNA was regulated by thyroid statuses but in opposite way compared to the manner in the thyroid gland. There were no extrathyroidal tissues that expressed all three characteristic genes of thyroid follicular cells.

Conclusions

NIS mRNA expression in the thyroid gland was up-regulated in hypothyroid mice and was down-regulated in hyperthyroid mice, suggesting that NIS mRNA in the thyroid gland is regulated by thyroid statuses. In contrast, NIS mRNA expression in extrathyroidal tissues was not altered by thyroid statuses although it was widely expressed. Lack of responsiveness of NIS mRNA expressions in extrathyroidal tissues reemphasizes additional functions of NIS protein in extrathyroidal tissues other than iodide trapping.
Appendix
Available only for authorised users
Literature
1.
go back to reference Dai G, Levy O, Carrasco N: Cloning and characterization of the thyroid iodide transporter. Nature 1996, 379: 458–460. 10.1038/379458a0PubMedCrossRef Dai G, Levy O, Carrasco N: Cloning and characterization of the thyroid iodide transporter. Nature 1996, 379: 458–460. 10.1038/379458a0PubMedCrossRef
2.
go back to reference Smanik PA, Liu Q, Furminger TL, Ryu K, Xing S, Mazzaferri EL, Jhiang SM: Cloning of the human sodium lodide symporter. Biochem Biophys Res Commun 1996, 226: 339–345. 10.1006/bbrc.1996.1358PubMedCrossRef Smanik PA, Liu Q, Furminger TL, Ryu K, Xing S, Mazzaferri EL, Jhiang SM: Cloning of the human sodium lodide symporter. Biochem Biophys Res Commun 1996, 226: 339–345. 10.1006/bbrc.1996.1358PubMedCrossRef
3.
go back to reference Perron B, Rodriguez AM, Leblanc G, Pourcher T: Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues. J Endocrinol 2001, 170: 185–196. 10.1677/joe.0.1700185PubMedCrossRef Perron B, Rodriguez AM, Leblanc G, Pourcher T: Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues. J Endocrinol 2001, 170: 185–196. 10.1677/joe.0.1700185PubMedCrossRef
4.
go back to reference Fujiwara H, Tatsumi K, Miki K, Harada T, Miyai K, Takai S, Amino N: Congenital hypothyroidism caused by a mutation in the Na+/I- symporter. Nat Genet 1997, 16: 124–125. 10.1038/ng0697-124PubMedCrossRef Fujiwara H, Tatsumi K, Miki K, Harada T, Miyai K, Takai S, Amino N: Congenital hypothyroidism caused by a mutation in the Na+/I- symporter. Nat Genet 1997, 16: 124–125. 10.1038/ng0697-124PubMedCrossRef
5.
go back to reference Matsuda A, Kosugi S: A homozygous missense mutation of the sodium/iodide symporter gene causing iodide transport defect. J Clin Endocrinol Metab 1997, 82: 3966–3971. 10.1210/jc.82.12.3966PubMed Matsuda A, Kosugi S: A homozygous missense mutation of the sodium/iodide symporter gene causing iodide transport defect. J Clin Endocrinol Metab 1997, 82: 3966–3971. 10.1210/jc.82.12.3966PubMed
6.
go back to reference Levy O, Dai G, Riedel C, Ginter CS, Paul EM, Lebowitz AN, Carrasco N: Characterization of the thyroid Na+/I- symporter with an anti-COOH terminus antibody. Proc Natl Acad Sci USA 1997, 94: 5568–5573. 10.1073/pnas.94.11.5568PubMedCentralPubMedCrossRef Levy O, Dai G, Riedel C, Ginter CS, Paul EM, Lebowitz AN, Carrasco N: Characterization of the thyroid Na+/I- symporter with an anti-COOH terminus antibody. Proc Natl Acad Sci USA 1997, 94: 5568–5573. 10.1073/pnas.94.11.5568PubMedCentralPubMedCrossRef
7.
go back to reference Saito T, Endo T, Kawaguchi A, Ikeda M, Nakazato M, Kogai T, Onaya T: Increased expression of the Na+/I- symporter in cultured human thyroid cells exposed to thyrotropin and in Graves' thyroid tissue. J Clin Endocrinol Metab 1997, 82: 3331–3336. 10.1210/jc.82.10.3331PubMed Saito T, Endo T, Kawaguchi A, Ikeda M, Nakazato M, Kogai T, Onaya T: Increased expression of the Na+/I- symporter in cultured human thyroid cells exposed to thyrotropin and in Graves' thyroid tissue. J Clin Endocrinol Metab 1997, 82: 3331–3336. 10.1210/jc.82.10.3331PubMed
8.
go back to reference Endo T, Kaneshige M, Nakazato M, Ohmori M, Harii N, Onaya T: Thyroid transcription factor-1 activates the promoter activity of rat thyroid Na+/I- symporter gene. Mol Endocrinol 1997, 11: 1747–1755. 10.1210/me.11.11.1747PubMed Endo T, Kaneshige M, Nakazato M, Ohmori M, Harii N, Onaya T: Thyroid transcription factor-1 activates the promoter activity of rat thyroid Na+/I- symporter gene. Mol Endocrinol 1997, 11: 1747–1755. 10.1210/me.11.11.1747PubMed
9.
go back to reference Ohno M, Zannini M, Levy O, Carrasco N, di Lauro R: The paired-domain transcription factor Pax8 binds to the upstream enhancer of the rat sodium/iodide symporter gene and participates in both thyroid-specific and cyclic-AMP-dependent transcription. Mol Cell Biol 1999, 19: 2051–2060.PubMedCentralPubMed Ohno M, Zannini M, Levy O, Carrasco N, di Lauro R: The paired-domain transcription factor Pax8 binds to the upstream enhancer of the rat sodium/iodide symporter gene and participates in both thyroid-specific and cyclic-AMP-dependent transcription. Mol Cell Biol 1999, 19: 2051–2060.PubMedCentralPubMed
10.
go back to reference Smanik PA, Ryu KY, Theil KS, Mazzaferri EL, Jhiang SM: Expression, exon-intron organization, and chromosome mapping of the human sodium iodide symporter. Endocrinology 1997, 138: 3555–3558. 10.1210/en.138.8.3555PubMedCrossRef Smanik PA, Ryu KY, Theil KS, Mazzaferri EL, Jhiang SM: Expression, exon-intron organization, and chromosome mapping of the human sodium iodide symporter. Endocrinology 1997, 138: 3555–3558. 10.1210/en.138.8.3555PubMedCrossRef
11.
go back to reference Spitzweg C, Joba W, Eisenmenger W, Heufelder AE: Analysis of human sodium iodide symporter gene expression in extrathyroidal tissues and cloning of its complementary deoxyribonucleic acids from salivary gland, mammary gland, and gastric mucosa. J Clin Endocrinol Metab 1998, 83: 1746–1751. 10.1210/jc.83.5.1746PubMedCrossRef Spitzweg C, Joba W, Eisenmenger W, Heufelder AE: Analysis of human sodium iodide symporter gene expression in extrathyroidal tissues and cloning of its complementary deoxyribonucleic acids from salivary gland, mammary gland, and gastric mucosa. J Clin Endocrinol Metab 1998, 83: 1746–1751. 10.1210/jc.83.5.1746PubMedCrossRef
12.
go back to reference De La Vieja A, Dohan O, Levy O, Carrasco N: Molecular analysis of the sodium/iodide symporter: impact on thyroid and extrathyroid pathophysiology. Physiol Rev 2000, 80: 1083–1105.PubMed De La Vieja A, Dohan O, Levy O, Carrasco N: Molecular analysis of the sodium/iodide symporter: impact on thyroid and extrathyroid pathophysiology. Physiol Rev 2000, 80: 1083–1105.PubMed
13.
go back to reference Nicola JP, Basquin C, Portulano C, Reyna-Neyra A, Paroder M, Carrasco N: The Na+/I- symporter mediates active iodide uptake in the intestine. Am J Physiol Cell Physiol 2009, 296: C654–662. 10.1152/ajpcell.00509.2008PubMedCentralPubMedCrossRef Nicola JP, Basquin C, Portulano C, Reyna-Neyra A, Paroder M, Carrasco N: The Na+/I- symporter mediates active iodide uptake in the intestine. Am J Physiol Cell Physiol 2009, 296: C654–662. 10.1152/ajpcell.00509.2008PubMedCentralPubMedCrossRef
14.
go back to reference Tazebay UH, Wapnir IL, Levy O, Dohan O, Zuckier LS, Zhao QH, Deng HF, Amenta PS, Fineberg S, Pestell RG, et al.: The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat Med 2000, 6: 871–878. 10.1038/78630PubMedCrossRef Tazebay UH, Wapnir IL, Levy O, Dohan O, Zuckier LS, Zhao QH, Deng HF, Amenta PS, Fineberg S, Pestell RG, et al.: The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat Med 2000, 6: 871–878. 10.1038/78630PubMedCrossRef
15.
go back to reference Kogai T, Taki K, Brent GA: Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr Relat Cancer 2006, 13: 797–826. 10.1677/erc.1.01143PubMedCrossRef Kogai T, Taki K, Brent GA: Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr Relat Cancer 2006, 13: 797–826. 10.1677/erc.1.01143PubMedCrossRef
16.
go back to reference Wapnir IL, van de Rijn M, Nowels K, Amenta PS, Walton K, Montgomery K, Greco RS, Dohan O, Carrasco N: Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections. J Clin Endocrinol Metab 2003, 88: 1880–1888. 10.1210/jc.2002-021544PubMedCrossRef Wapnir IL, van de Rijn M, Nowels K, Amenta PS, Walton K, Montgomery K, Greco RS, Dohan O, Carrasco N: Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections. J Clin Endocrinol Metab 2003, 88: 1880–1888. 10.1210/jc.2002-021544PubMedCrossRef
17.
go back to reference Brown-Grant K: Extrathyroidal iodide concentrating mechanisms. Physiol Rev 1961, 41: 189–293. Brown-Grant K: Extrathyroidal iodide concentrating mechanisms. Physiol Rev 1961, 41: 189–293.
18.
go back to reference Dohan O, De la Vieja A, Paroder V, Riedel C, Artani M, Reed M, Ginter CS, Carrasco N: The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance. Endocr Rev 2003, 24: 48–77. 10.1210/er.2001-0029PubMedCrossRef Dohan O, De la Vieja A, Paroder V, Riedel C, Artani M, Reed M, Ginter CS, Carrasco N: The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance. Endocr Rev 2003, 24: 48–77. 10.1210/er.2001-0029PubMedCrossRef
19.
go back to reference Wapnir IL, Goris M, Yudd A, Dohan O, Adelman D, Nowels K, Carrasco N: The Na+/I- symporter mediates iodide uptake in breast cancer metastases and can be selectively down-regulated in the thyroid. Clin Cancer Res 2004, 10: 4294–4302. 10.1158/1078-0432.CCR-04-0074PubMedCrossRef Wapnir IL, Goris M, Yudd A, Dohan O, Adelman D, Nowels K, Carrasco N: The Na+/I- symporter mediates iodide uptake in breast cancer metastases and can be selectively down-regulated in the thyroid. Clin Cancer Res 2004, 10: 4294–4302. 10.1158/1078-0432.CCR-04-0074PubMedCrossRef
20.
go back to reference Yaffe SJ, Bierman CW, Cann HM, Cohen SN, Freeman J, Segal S, Soyka LF, Weiss CF, Ballin JC, Done AK, Del Prato PS, Farchione L, Kretchmer N, Oakley G, Sawchuk S, Scott CP, Simopoulos AP, Chudzik G: Adverse reactions to iodide therapy of asthma and other pulmonary diseases. Pediatrics 1976, 57: 272–274. Yaffe SJ, Bierman CW, Cann HM, Cohen SN, Freeman J, Segal S, Soyka LF, Weiss CF, Ballin JC, Done AK, Del Prato PS, Farchione L, Kretchmer N, Oakley G, Sawchuk S, Scott CP, Simopoulos AP, Chudzik G: Adverse reactions to iodide therapy of asthma and other pulmonary diseases. Pediatrics 1976, 57: 272–274.
21.
go back to reference Lopez-Belio M, Henderson WJ, Mansueto M, Holinger PH: The concentration of I 131 in the bronchial tree after oral administration of tagged Cal 2 and KI. Dis Chest 1961, 39: 158–161. 10.1378/chest.39.2.158PubMedCrossRef Lopez-Belio M, Henderson WJ, Mansueto M, Holinger PH: The concentration of I 131 in the bronchial tree after oral administration of tagged Cal 2 and KI. Dis Chest 1961, 39: 158–161. 10.1378/chest.39.2.158PubMedCrossRef
Metadata
Title
Effect of thyroid statuses on sodium/iodide symporter (NIS) gene expression in the extrathyroidal tissues in mice
Authors
Md Harun-Or-Rashid
Masato Asai
Xiao-yang Sun
Yoshitaka Hayashi
Junichi Sakamoto
Yoshiharu Murata
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Thyroid Research / Issue 1/2010
Electronic ISSN: 1756-6614
DOI
https://doi.org/10.1186/1756-6614-3-3

Other articles of this Issue 1/2010

Thyroid Research 1/2010 Go to the issue