Endocrine Disruptors and the Thyroid Gland—A Combined in Vitro and in Vivo Analysis of Potential New Biomarkers

Abstract

BackgroundThere 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.Objective and MethodsWe 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.ResultsIn 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.ConclusionsAs 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.

Bioconcentration and metabolism of BDE-209 in the presence of titanium dioxide nanoparticles and impact on the thyroid endocrine system and neuronal development in zebrafish larvae

“…expression is a useful biomarker of thyroid system function (Schmutzler et al, 2007). However, we did not observe the expected downregulation of tsh in the larvae from either the BDE-209 or nano-TiO 2 co-exposed groups.…”

Exposure of zebrafish embryos/larvae to TDCPP alters concentrations of thyroid hormones and transcriptions of genes involved in the hypothalamic–pituitary–thyroid axis

“…TSH is encoded by the gene tshˇ. It has been demonstrated that tshˇ expression is a useful biomarker of the function of the thyroid system (Kratzsch and Pulzer, 2008;Schmutzler et al, 2007). In the present study, mRNA expression of tshˇ was significantly upregulated after TDCPP exposure.…”

Serum retinol-binding protein 4 levels in nonobese women with polycystic ovary syndrome

“…Especially for TSH, the research by Choi et al (26) had suggested that RBP4 levels were associated with subclinical hypothyroidism. The retinol-binding protein is easily filtered through the kidney, forming a complex with transthyretin, a transport protein for T 4 , and this complex can prevent retinol-binding protein from being cleared by the kidney (33,34). It is possible that thyroid function could influence the excretion of RBP4 from the kidney.…”