ECE2014 Poster Presentations Endocrine disruptors (12 abstracts)
Di-ethylhexyl-phthalate is metabolised by human thyroid cells and may influence thyroglobulin secretion
Juliana Frohnert Hansen 1 , Marianne Møller Brorson 1 , Marie-Louise Hartoft-Nielsen 1 , Malene Boas 2 , Katharina M Main 2 , Hanne Frederiksen 2 , Jacob Hofman-Bang 1 , Æse Krogh Rasmussen 1 & Ulla Feldt-Rasmussen 1
1Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 2Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Introduction: Phthalates are suspected to influence thyroid function in epidemiologic and experimental animal studies. The aim of the study was to investigate the ability of primary human thyroid cell cultures to metabolise phthalates and a possible concentration-dependent response of phthalates on thyroglobulin (Tg) secretion.
Methods: Human thyrocytes obtained from thyroidectomies were cultured to confluent monolayers. These were exposed to DEHP in concentrations 10−9 to 10−4 M, with TSH (1 IU/l) for 24, 48 or 72 h. DEHP metabolites and Tg were quantified in the cell supernatants (liquid chromatography–tandem mass spectrometry and ELISA respectively). Results are shown as mean±S.D. and statistical analyses were performed using two-way ANOVA (SAS Institute).
Results: Cell cultures metabolised DEHP (10−7−10−4 M) to its primary metabolite mono-ethylhexyl-phthalate (MEHP). The conversion analysed as metabolite concentration after 72 h exposure varied depending on the DEHP-concentration added, from 1.2±0.6% at 10−4 M, to 72.8±21.2% at 10−7 M DEHP (n=three cultures from one individual).
No influence was found on TSH-stimulated Tg-secretion after 72 h DEHP exposure (10−9 to 10−4 M) (P=0.86, n= five cell cultures in single determination) compared to controls and independent of the concentration of DEHP used. Preliminary results, however, suggested an inhibitory influence to occur sooner, i.e. after 24 h compared to 48 and 72 h (n=one cell culture in single determination).
Conclusion: DEHP is internalised and metabolised by primary human thyroid cell cultures. The relative conversion, however, decreased inversely proportional to the DEHP concentration added, indicating an active saturable process in the thyroid cells. Preliminary studies indicated a DEHP-mediated decrease in Tg-secretion after 24 h. This finding is currently investigated further. On the other hand, no significant effect on Tg-secretion could be detected after 72 h exposure. Supplementary studies on DEHP-metabolism at earlier time points also need further investigation.
Volume 35
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