Exp Clin Endocrinol Diabetes 2006; 114 - OR8_44
DOI: 10.1055/s-2006-932882

Thyroid hormone biosynthesis is a sensitive target for the action of endocrine disrupting chemicals (EDC)

C Schmutzler 1, A Bacinski 1, P Ambrugger 2, K Huhne 1, A Grüters 2, J Köhrle 1
  • 1Charité, Universitätsmedizin Berlin, Institut für Experimentelle Endokrinologie, Berlin, Germany
  • 2Charité, Universitätsmedizin Berlin, Institut für Experimentelle Pädiatrische Endokrinologie, Berlin, Germany

Objectives: EDC, deriving either from plants or from industrial products, disturb regulation of both the reproductive and the thyroid endocrine axis, too. We here screened for effects of suspected EDC on thyroid hormone (TH) biosynthesis.

Methods: Interference with iodide uptake was examined using rat FRTL-5 thyroid cells which express sodium iodide symporter. Effects on human thyroperoxidase (TPO) activity were measured using the guaiacol oxidation, iodide oxidation and tyrosine iodination assays in extracts prepared from human FTC-238 cells stably transfected with human TPO. EDC examined were: genistein, silymarin and resveratrol [plant polyphenols]; 4-methylbenzylidene-camphor (4-MBC), octyl-methoxycinnamate (OMC), benzophenone 2 and 3 (BP2 and 3) [UV filters]; bisphenol A, 4-nonylphenol and dibutylphtalate [components of plastic materials]; linuron [pesticide]; 17β-estradiol benzoate and 5α-androstane-3β,17β-diol [estrogen receptor ligands] and F21388 [synthetic flavonoid].

Results: Genistein, silymarin, resveratrol, BP2, bisphenol A, 4-nonylphenol and F21388 inhibited TPO activity dose-dependently with IC50 values ranging from 0.37 to 174µmol/L. Iodide uptake was inhibited by genistein and 4-nonylphenol at 10µmol/L and by OMC and 4-MBC at 0.1 and 1.0µmol/L. Genistein, F21388 and BP2 in combination with H2O2 inactivated TPO, an effect that was prevented if adequate iodide concentrations were present in the reaction mixture. In rats, 4-MBC administration caused goiter (Schlumpf et al., Toxicology, 2004) and BP2 a decrease in serum T4 accompanied by an increase in TSH (Jarry et al., Toxicology, 2004).

Conclusions: Our data indicate that EDC may interfere with hormone biosynthesis in the thyroid gland and thereby display a goitrogenic action especially in the context of inadequate iodide supply. This may have consequences for human health especially on the background of a still prevailing deficiency in the supply of the essential trace element iodide in many parts of the world. -

Supported by EU grants