Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro

Juliana Frohnert Hansen; Marianne Møller Brorson; Malene Boas; Hanne Frederiksen; Claus Henrik Nielsen; Emma Sofie Lindström; Jacob Hofman-Bang; Marie-Louise Hartoft-Nielsen; Thomas Frisch; Katharina M Main; Klaus Bendtzen; Åse Krogh Rasmussen; Ulla Feldt-Rasmussen

doi:10.1371/journal.pone.0151192

Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro

Juliana Frohnert Hansen, Marianne Møller Brorson, Malene Boas, Hanne Frederiksen, Claus Henrik Nielsen, Emma Sofie Lindström, Jacob Hofman-Bang, Marie-Louise Hartoft-Nielsen, Thomas Frisch, Katharina M Main, Klaus Bendtzen, Åse Krogh Rasmussen, Ulla Feldt-Rasmussen

11 Citations (Scopus)

Abstract

Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP)) and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate (MEHP)) on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg) secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor) by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells.

Original language	English
Article number	e0151192
Journal	P L o S One
Volume	11
Issue number	3
Number of pages	16
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0151192
Publication status	Published - Mar 2016

Keywords

Cells, Cultured
Cyclic AMP
Dibutyl Phthalate
Diethylhexyl Phthalate
Humans
Phthalic Acids
Plasticizers
Thyroglobulin
Thyroid Gland
Journal Article
Research Support, Non-U.S. Gov't

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Hansen, J. F., Brorson, M. M., Boas, M., Frederiksen, H., Nielsen, C. H., Lindström, E. S., Hofman-Bang, J., Hartoft-Nielsen, M.-L., Frisch, T., Main, K. M., Bendtzen, K., Rasmussen, Å. K., & Feldt-Rasmussen, U. (2016). Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro. P L o S One, 11(3), Article e0151192. https://doi.org/10.1371/journal.pone.0151192

Hansen, JF, Brorson, MM, Boas, M, Frederiksen, H, Nielsen, CH, Lindström, ES, Hofman-Bang, J, Hartoft-Nielsen, M-L, Frisch, T, Main, KM, Bendtzen, K, Rasmussen, ÅK & Feldt-Rasmussen, U 2016, 'Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro', P L o S One, vol. 11, no. 3, e0151192. https://doi.org/10.1371/journal.pone.0151192

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title = "Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro",

abstract = "Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP)) and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate (MEHP)) on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg) secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor) by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells.",

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T1 - Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro

AU - Hansen, Juliana Frohnert

AU - Brorson, Marianne Møller

AU - Boas, Malene

AU - Frederiksen, Hanne

AU - Nielsen, Claus Henrik

AU - Lindström, Emma Sofie

AU - Hofman-Bang, Jacob

AU - Hartoft-Nielsen, Marie-Louise

AU - Frisch, Thomas

AU - Main, Katharina M

AU - Bendtzen, Klaus

AU - Rasmussen, Åse Krogh

AU - Feldt-Rasmussen, Ulla

PY - 2016/3

Y1 - 2016/3

N2 - Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP)) and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate (MEHP)) on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg) secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor) by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells.

AB - Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP)) and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate (MEHP)) on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg) secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor) by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells.

KW - Cells, Cultured

KW - Cyclic AMP

KW - Dibutyl Phthalate

KW - Diethylhexyl Phthalate

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KW - Phthalic Acids

KW - Plasticizers

KW - Thyroglobulin

KW - Thyroid Gland

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1371/journal.pone.0151192

DO - 10.1371/journal.pone.0151192

M3 - Journal article

C2 - 26985823

SN - 1932-6203

VL - 11

JO - P L o S One

JF - P L o S One

IS - 3

M1 - e0151192

ER -

Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro

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Keywords

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