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| Status |
Public on Jul 19, 2008 |
| Title |
Amiodarone effects on cultured human thyroid follicles |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Amiodarone reversibly decreases sodium-iodide symporter mRNA expression at therapeutic concentrations and induces antioxidant responses at supraphysiological concentrations in cultured human thyroid follicles
Amiodarone, a potent antiarrhythmic agent, is a highly active oxidant, exerting cytotoxic effects on thyrocytes at pharmacological concentrations. Patients receiving amiodarone usually remain euthyroid, but occasionally develop thyroid dysfunction, such as amiodarone-associated hypothyroidism or amiodarone-induced thyrotoxicosis. To elucidate the mechanism by which amiodarone elicits thyroid dysfunction, human thyroid follicles were cultured with TSH and amiodarone at therapeutic (1-2 microM) and pharmacological (10-20microM) concentrations, and the drug-induced effect on whole human gene expression was analyzed by cDNA microarray. Amiodarone at 1-2microM decreased the expression level of the sodium-iodide symporter (NIS) to nearly half, but did not affect genes participating in thyroid hormonogenesis (thyroid peroxidase, thyroglobulin, pendrin, NADPH oxidase). Higher concentrations (10-20 microM) decreased the expression of all these genes, accompanied by increased expression of antioxidant proteins such as heme oxygenase 1 and ferritin. When thyroid follicles obtained from a patient with Graves’ disease who had been treated with amiodarone for 2 months before thyroidectomy were cultured in amiodarone-free medium, TSH-induced thyroid function was intact, suggesting that amiodarone at a maintenance dose did not elicit any cytotoxic effect on thyrocytes. The ultrastructural features of cultured thyroid follicles were compatible with these in vitro findings. These in vitro and ex vivo findings suggest that patients taking maintenance doses of amiodarone usually remain euthyroid, probably due to escape from the Wolff-Chaikoff effect mediated by decreased expression of NIS mRNA. Furthermore, amiodarone is not cytotoxic for thyrocytes at therapeutic concentrations but elicits cytotoxicity through oxidant activity at supra-physiological concentrations.
Keywords: Cultured human thyroid follicles
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| Overall design |
Two condition experiment, control vs. Amiodarone 1 and 10 microM, cultured for 5 days
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| Contributor(s) |
Sato K, Yamazaki K |
| Citation(s) |
18020914 |
| Submission date |
Jul 18, 2008 |
| Last update date |
Dec 06, 2012 |
| Contact name |
Kanji Sato |
| E-mail(s) |
satokan@attglobal.net
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| Phone |
81-3-3353-8111
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| Fax |
81-3-3354-3706
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| Organization name |
Tokyo Women's Medical University
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| Department |
Institute of Clinical Endocrinology
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| Lab |
Department of Medicine
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| Street address |
Kawada-cho 8-1
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| City |
Shinjuku-ku |
| State/province |
Tokyo |
| ZIP/Postal code |
162-8666 |
| Country |
Japan |
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| Platforms (1) |
| GPL1708 |
Agilent-012391 Whole Human Genome Oligo Microarray G4112A (Feature Number version) |
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| Samples (2) |
| GSM306251 |
Thyroid tissue cultured with 10 microM amiodarone medium for 5 days |
| GSM307136 |
Thyroid tissue cultured with 1 microM amiodarone medium for 5 days |
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| Relations |
| BioProject |
PRJNA113455 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE12164_RAW.tar |
26.1 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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