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The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro

BACKGROUND: Normal thyroid function is essential for general growth and metabolism, but can be affected by endocrine disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs) have been used worldwide to reduce flammability in different materials and are suspected to be EDCs. The production...

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Autores principales: Kronborg, Thit Mynster, Hansen, Juliana Frohnert, Rasmussen, Åse Krogh, Vorkamp, Katrin, Nielsen, Claus Henrik, Frederiksen, Marie, Hofman-Bang, Jacob, Hahn, Christoffer Holst, Ramhøj, Louise, Feldt-Rasmussen, Ulla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482471/
https://www.ncbi.nlm.nih.gov/pubmed/28644858
http://dx.doi.org/10.1371/journal.pone.0179858
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author Kronborg, Thit Mynster
Hansen, Juliana Frohnert
Rasmussen, Åse Krogh
Vorkamp, Katrin
Nielsen, Claus Henrik
Frederiksen, Marie
Hofman-Bang, Jacob
Hahn, Christoffer Holst
Ramhøj, Louise
Feldt-Rasmussen, Ulla
author_facet Kronborg, Thit Mynster
Hansen, Juliana Frohnert
Rasmussen, Åse Krogh
Vorkamp, Katrin
Nielsen, Claus Henrik
Frederiksen, Marie
Hofman-Bang, Jacob
Hahn, Christoffer Holst
Ramhøj, Louise
Feldt-Rasmussen, Ulla
author_sort Kronborg, Thit Mynster
collection PubMed
description BACKGROUND: Normal thyroid function is essential for general growth and metabolism, but can be affected by endocrine disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs) have been used worldwide to reduce flammability in different materials and are suspected to be EDCs. The production of the commercial Penta- and OctaBDE mixtures is banned, but DecaBDEs and existing products may leak PBDEs into the environment. Our aim was to investigate the effect of the PentaBDE mixture DE-71 on human thyroid cells in vitro. MATERIALS AND METHODS: Primary human thyroid cells were obtained as paraadenomatous tissue and cultured in monolayers. The influence of DE-71 on cyclic adenosine monophosphate (cAMP) and thyroglobulin (Tg) production was examined in the culture medium by competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Real-time quantitative PCR analysis of thyroid-specific genes was performed on the exposed cell cultures. PBDE concentrations were determined in cellular and supernatant fractions of the cultures. RESULTS: DE-71 inhibited Tg-release from TSH-stimulated thyrocytes. At 50 mg/L DE-71, mean Tg production was reduced by 71.9% (range: 8.5–98.7%), and cAMP by 95.1% (range: 91.5–98.8%) compared to controls). Expression of mRNA encoding Tg, TPO and TSHr were significantly inhibited (p<0.0001, p = 0.0079, and p = 0.0002, respectively). The majority of DE-71 added was found in the cell fraction. No cytotoxicity was found. CONCLUSIONS: DE-71 inhibited differentiated thyroid cell functions in a two phase response manner and a concentration-dependent inhibition of Tg and cAMP production, respectively, as well as expression of mRNA encoding Tg, TPO and TSHr. Our findings suggest an inhibiting effect of PBDEs on thyroid cells.
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spelling pubmed-54824712017-07-06 The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro Kronborg, Thit Mynster Hansen, Juliana Frohnert Rasmussen, Åse Krogh Vorkamp, Katrin Nielsen, Claus Henrik Frederiksen, Marie Hofman-Bang, Jacob Hahn, Christoffer Holst Ramhøj, Louise Feldt-Rasmussen, Ulla PLoS One Research Article BACKGROUND: Normal thyroid function is essential for general growth and metabolism, but can be affected by endocrine disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs) have been used worldwide to reduce flammability in different materials and are suspected to be EDCs. The production of the commercial Penta- and OctaBDE mixtures is banned, but DecaBDEs and existing products may leak PBDEs into the environment. Our aim was to investigate the effect of the PentaBDE mixture DE-71 on human thyroid cells in vitro. MATERIALS AND METHODS: Primary human thyroid cells were obtained as paraadenomatous tissue and cultured in monolayers. The influence of DE-71 on cyclic adenosine monophosphate (cAMP) and thyroglobulin (Tg) production was examined in the culture medium by competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Real-time quantitative PCR analysis of thyroid-specific genes was performed on the exposed cell cultures. PBDE concentrations were determined in cellular and supernatant fractions of the cultures. RESULTS: DE-71 inhibited Tg-release from TSH-stimulated thyrocytes. At 50 mg/L DE-71, mean Tg production was reduced by 71.9% (range: 8.5–98.7%), and cAMP by 95.1% (range: 91.5–98.8%) compared to controls). Expression of mRNA encoding Tg, TPO and TSHr were significantly inhibited (p<0.0001, p = 0.0079, and p = 0.0002, respectively). The majority of DE-71 added was found in the cell fraction. No cytotoxicity was found. CONCLUSIONS: DE-71 inhibited differentiated thyroid cell functions in a two phase response manner and a concentration-dependent inhibition of Tg and cAMP production, respectively, as well as expression of mRNA encoding Tg, TPO and TSHr. Our findings suggest an inhibiting effect of PBDEs on thyroid cells. Public Library of Science 2017-06-23 /pmc/articles/PMC5482471/ /pubmed/28644858 http://dx.doi.org/10.1371/journal.pone.0179858 Text en © 2017 Kronborg et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kronborg, Thit Mynster
Hansen, Juliana Frohnert
Rasmussen, Åse Krogh
Vorkamp, Katrin
Nielsen, Claus Henrik
Frederiksen, Marie
Hofman-Bang, Jacob
Hahn, Christoffer Holst
Ramhøj, Louise
Feldt-Rasmussen, Ulla
The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro
title The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro
title_full The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro
title_fullStr The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro
title_full_unstemmed The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro
title_short The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro
title_sort flame retardant de-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482471/
https://www.ncbi.nlm.nih.gov/pubmed/28644858
http://dx.doi.org/10.1371/journal.pone.0179858
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