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.
authors.affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Juliana Frohnert
authors.initials: JF
authors.lastname: Hansen
authors.affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marianne Møller
authors.initials: MM
authors.lastname: Brorson
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Malene
authors.initials: M
authors.lastname: Boas
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Frederiksen
authors.affiliation: Institute for Inflammation Research, section 7521, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Claus Henrik
authors.initials: CH
authors.lastname: Nielsen
authors.affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Emma Sofie
authors.initials: ES
authors.lastname: Lindström
authors.affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hofman-Bang
authors.affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Hartoft-Nielsen
authors.affiliation: Department of ENT-Head and Neck surgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Frisch
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Main
authors.affiliation: Institute for Inflammation Research, section 7521, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Åse Krogh
authors.initials: ÅK
authors.lastname: Rasmussen
authors.affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Feldt-Rasmussen
mesh_terms: D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003993:Dibutyl Phthalate / Q000378:metabolism* / Q000633:toxicity; D004051:Diethylhexyl Phthalate / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D010795:Phthalic Acids / Q000378:metabolism* / Q000633:toxicity; D010968:Plasticizers / Q000378:metabolism* / Q000633:toxicity; D013954:Thyroglobulin / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D010795:Phthalic Acids; D010968:Plasticizers; D003993:Dibutyl Phthalate; D013954:Thyroglobulin; D004051:Diethylhexyl Phthalate; D000242:Cyclic AMP; C007379:diethyl phthalate; C028577:monobutyl phthalate