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

• Published in: PloS one 2016-03, Vol.11 (3), p.e0151192-e0151192
• Main Authors: Hansen, Juliana Frohnert, Brorson, Marianne Møller, Boas, Malene, Frederiksen, Hanne, Nielsen, Claus Henrik, Lindström, Emma Sofie, Hofman-Bang, Jacob, Hartoft-Nielsen, Marie-Louise, Frisch, Thomas, Main, Katharina M, Bendtzen, Klaus, Rasmussen, Åse Krogh, Feldt-Rasmussen, Ulla
• Format: Article
• Language: English
• Subjects: Adenosine; Adenosine monophosphate; Analysis; Biology and Life Sciences; Biotechnology; Butyl phthalate; Cell culture; Cell death; Cells, Cultured; Cyclic AMP; Cyclic AMP - metabolism; Cytokines; Dibutyl Phthalate - metabolism; Dibutyl Phthalate - toxicity; Diesters; Diethylhexyl Phthalate - metabolism; Diethylhexyl Phthalate - toxicity; Epidemiology; Experiments; Exposure; Gangrene; Gene expression; Hormones; Humans; Iodide peroxidase; Iodine; Kinetics; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Medicine and Health Sciences; Metabolism; Metabolites; n-Butyl phthalate; Peroxidase; Phthalate esters; Phthalates; Phthalic Acids - metabolism; Phthalic Acids - toxicity; Physical Sciences; Physiological aspects; Plasticizers - metabolism; Plasticizers - toxicity; Research and Analysis Methods; Secretion; Sodium; Studies; Thyroglobulin; Thyroglobulin - metabolism; Thyroid; Thyroid gland; Thyroid Gland - cytology; Thyroid Gland - drug effects; Thyroid Gland - metabolism; Thyroid hormones; Tumor necrosis factor-TNF; Urine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0151192

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.