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Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points
Organic iodides have been shown to induce thyroid hypertrophy and increase alterations in colloid in rats, although the mechanism involved in this toxicity is unclear. To evaluate the effect that free iodide has on thyroid toxicity, we exposed rats for 2 weeks by daily gavage to sodium iodide (NaI)....
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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National Institute of Environmental Health Sciences
2005
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1281279/ https://www.ncbi.nlm.nih.gov/pubmed/16203246 http://dx.doi.org/10.1289/ehp.7690 |
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author | Glatt, Christine M. Ouyang, Ming Welsh, William Green, John W. Connor, John O Frame, Steven R. Everds, Nancy E. Poindexter, Greg Snajdr, Suzanne Delker, Don A. |
author_facet | Glatt, Christine M. Ouyang, Ming Welsh, William Green, John W. Connor, John O Frame, Steven R. Everds, Nancy E. Poindexter, Greg Snajdr, Suzanne Delker, Don A. |
author_sort | Glatt, Christine M. |
collection | PubMed |
description | Organic iodides have been shown to induce thyroid hypertrophy and increase alterations in colloid in rats, although the mechanism involved in this toxicity is unclear. To evaluate the effect that free iodide has on thyroid toxicity, we exposed rats for 2 weeks by daily gavage to sodium iodide (NaI). To compare the effects of compounds with alternative mechanisms (increased thyroid hormone metabolism and decreased thyroid hormone synthesis, respectively), we also examined phenobarbital (PB) and propylthiouracil (PTU) as model thyroid toxicants. Follicular cell hypertrophy and pale-staining colloid were present in thyroid glands from PB-treated rats, and more severe hypertrophy/colloid changes along with diffuse hyperplasia were present in thyroid glands from PTU-treated rats. In PB-and PTU-treated rats, thyroid-stimulating hormone (TSH) levels were significantly elevated, and both thyroxine and triiodothyronine hormone levels were significantly decreased. PB induced hepatic uridine diphosphate-glucuronyltransferase (UDPGT) activity almost 2-fold, whereas PTU reduced hepatic 5′-deiodinase I (5′-DI) activity to < 10% of control in support of previous reports regarding the mechanism of action of each chemical. NaI also significantly altered liver weights and UDPGT activity but did not affect thyroid hormone levels or thyroid pathology. Thyroid gene expression analyses using Affymetrix U34A GeneChips, a regularized t-test, and Gene Map Annotator and Pathway Profiler demonstrated significant changes in rhodopsin-like G-protein–coupled receptor transcripts from all chemicals tested. NaI demonstrated dose-dependent changes in multiple oxidative stress–related genes, as also determined by principal component and linear regression analyses. Differential transcript profiles, possibly relevant to rodent follicular cell tumor outcomes, were observed in rats exposed to PB and PTU, including genes involved in Wnt signaling and ribosomal protein expression. |
format | Text |
id | pubmed-1281279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | National Institute of Environmental Health Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-12812792005-11-30 Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points Glatt, Christine M. Ouyang, Ming Welsh, William Green, John W. Connor, John O Frame, Steven R. Everds, Nancy E. Poindexter, Greg Snajdr, Suzanne Delker, Don A. Environ Health Perspect Research Organic iodides have been shown to induce thyroid hypertrophy and increase alterations in colloid in rats, although the mechanism involved in this toxicity is unclear. To evaluate the effect that free iodide has on thyroid toxicity, we exposed rats for 2 weeks by daily gavage to sodium iodide (NaI). To compare the effects of compounds with alternative mechanisms (increased thyroid hormone metabolism and decreased thyroid hormone synthesis, respectively), we also examined phenobarbital (PB) and propylthiouracil (PTU) as model thyroid toxicants. Follicular cell hypertrophy and pale-staining colloid were present in thyroid glands from PB-treated rats, and more severe hypertrophy/colloid changes along with diffuse hyperplasia were present in thyroid glands from PTU-treated rats. In PB-and PTU-treated rats, thyroid-stimulating hormone (TSH) levels were significantly elevated, and both thyroxine and triiodothyronine hormone levels were significantly decreased. PB induced hepatic uridine diphosphate-glucuronyltransferase (UDPGT) activity almost 2-fold, whereas PTU reduced hepatic 5′-deiodinase I (5′-DI) activity to < 10% of control in support of previous reports regarding the mechanism of action of each chemical. NaI also significantly altered liver weights and UDPGT activity but did not affect thyroid hormone levels or thyroid pathology. Thyroid gene expression analyses using Affymetrix U34A GeneChips, a regularized t-test, and Gene Map Annotator and Pathway Profiler demonstrated significant changes in rhodopsin-like G-protein–coupled receptor transcripts from all chemicals tested. NaI demonstrated dose-dependent changes in multiple oxidative stress–related genes, as also determined by principal component and linear regression analyses. Differential transcript profiles, possibly relevant to rodent follicular cell tumor outcomes, were observed in rats exposed to PB and PTU, including genes involved in Wnt signaling and ribosomal protein expression. National Institute of Environmental Health Sciences 2005-10 2005-05-12 /pmc/articles/PMC1281279/ /pubmed/16203246 http://dx.doi.org/10.1289/ehp.7690 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright. |
spellingShingle | Research Glatt, Christine M. Ouyang, Ming Welsh, William Green, John W. Connor, John O Frame, Steven R. Everds, Nancy E. Poindexter, Greg Snajdr, Suzanne Delker, Don A. Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points |
title | Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points |
title_full | Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points |
title_fullStr | Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points |
title_full_unstemmed | Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points |
title_short | Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points |
title_sort | molecular characterization of thyroid toxicity: anchoring gene expression profiles to biochemical and pathologic end points |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1281279/ https://www.ncbi.nlm.nih.gov/pubmed/16203246 http://dx.doi.org/10.1289/ehp.7690 |
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