Endocrine disruptors and the thyroid gland--a combined in vitro and in vivo analysis of potential new biomarkers

There is growing evidence that, in addition to the reproductive system, the hypothalamic-pituitary-thyroid axis is a target of endocrine-disrupting compounds (EDCs). However, this is not reflected adequately in current screening and assessment procedures for endocrine activity that to date determine...

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Published in:	Environmental health perspectives Vol. 115 Suppl 1; no. Suppl 1; pp. 77 - 83
Main Authors:	Schmutzler, Cornelia, Gotthardt, Inka, Hofmann, Peter J, Radovic, Branislav, Kovacs, Gabor, Stemmler, Luise, Nobis, Inga, Bacinski, Anja, Mentrup, Birgit, Ambrugger, Petra, Grüters, Annette, Malendowicz, Ludwik K, Christoffel, Julie, Jarry, Hubertus, Seidlovà-Wuttke, Dana, Wuttke, Wolfgang, Köhrle, Josef
Format:	Journal Article
Language:	English
Published:	United States National Institute of Environmental Health Sciences 01-12-2007
Subjects:	Animals Biomarkers Cell Line Endocrine Disruptors - toxicity Female In Vitro Techniques Iodide Peroxidase - drug effects Iodide Peroxidase - metabolism Iodine - metabolism Malate Dehydrogenase - drug effects Malate Dehydrogenase - metabolism Rats Rats, Sprague-Dawley Thyroid Gland - drug effects Thyroid Gland - metabolism Thyroid Hormones - metabolism Thyrotropin - blood Thyrotropin - drug effects pituitary transthyretin thyroid peroxidase thyroid gland UV filters malic enzyme flavonoids sodium iodide symporter deiodinase
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Summary:	There is growing evidence that, in addition to the reproductive system, the hypothalamic-pituitary-thyroid axis is a target of endocrine-disrupting compounds (EDCs). However, this is not reflected adequately in current screening and assessment procedures for endocrine activity that to date determine only general parameters of thyroid function. We used several in vitro and ex vivo assays in an attempt to identify suitable biomarkers for antithyroid action testing a selected panel of putative EDCs. In vitro we detected stimulation or inhibition of iodide uptake into FRTL-5 rat thyroid cells, inhibition of thyroid hormone binding to transthyretin, agonistic or antagonistic effects in a thyroid hormone receptor-dependent reporter assay, and inhibition of thyroid peroxidase using a novel assay system based on human recombinant thyroperoxidase that might be suitable for routine screening for potential EDCs. In rats, chronic application of several EDCs led to changes in thyroid morphology, alterations of thyrotropin and thyroid hormone serum levels as well as alterations in peripheral thyroid hormone-regulated end points such as malic enzyme and type I 5'-deiodinase activity. As the effects of EDCs do not reflect classic mechanisms of hormone-dependent regulation and feedback, we believe multitarget and multimodal actions of EDCs affect the hypothalamic-pituitary-thyroid axis. These complex effects require a diverse approach for screening, evaluation, and risk assessment of potential antithyroid compounds. This approach involves novel in vitro or cell-based screening assays in order to assess thyroid hormone synthesis, transport, metabolism, and action as well as in vivo assays to measure thyroid hormone-regulated tissue-specific and developmental end points in animals.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors declare they have no competing financial interests.
ISSN:	0091-6765 1552-9924
DOI:	10.1289/ehp.9369