PARENT SESSION
18 - Endocrine Disruption
8:00 AM to 6:30 PM, Monday, 13 May 2002
Exhibition Area

(18-58) Thyroid hormone status in Danio rerio after exposure to methimazole.

Simon, Rupert¹, Hollósi, László^*,1, Michalke, Bernhard¹, Kettrup, Antonius^1,2, Schramm, Karl-Werner¹, ¹ GSF - Institute of Ecological Chemistry, Oberschleißheim, Germany² Technical University of Munich, Freising-Weihenstephan, Germany

ABSTRACT- Disruption of thyroid function by xenobiotic chemicals is an important ecological issue. Disruption of the thyroid-axis leads to severe developmental disorders (e.g. no eye rotation in flounder and hindered fin development in zebrafish larvae). Thyroid hormone (TH) homeostasis and action can be disrupted at several sites in the synthetic and elimination pathways. In fact, xenobiotic chemicals, which are known to interfere with normal thyroid function, have been shown to act primarily by (1) up-regulation of catabolism of TH, (2) inhibition of iodide uptake, (3) inhibition of TH synthesis, or (4) inhibition and/or up-regulation of deiodinases. Disturbance of the oestrogen-axis and feminisation in fish has been reported for repeatedly. Synergistic estrogenic effects of chemicals and/or exposure media are indicated by high vitellogenin concentrations in male fish. Inversely, antagonistic estrogenic effects may be shown by low vitellogenin concentrations in females. In this study we evaluate vitellogenin levels as molecular indicator for the impact of thyroid disorders on the oestrogen-axis. To monitor the actual exposure concentrations a method for quantification of methimazole in whole body homogenate based on RP-HPLC has been developed. Methimazole exposure concentrations are monitored by HPLC-UV-vis in the water body and whole body homogenates of exposed fish. For the determination of the TH-related substances (iodide, T4 and T3, reverse T3 (rT3), and the TH precursors monoiodotyrosine (MIT) and diiodotyrosine (DIT)) and vitellogenin we used existing HPLC/ICP-MS and immunochemical methods, respectively. We exposed adult D. rerio to six different concentrations of methimazole for three weeks and studied the concentrations of (A) methimazole and metabolites, (B) thyroid hormones and precursors, and (C) vitellogenin in whole body homogenates. Exposure-response relationships were determined.

Key words: danio rerio, thyroid, vitellogenin, methimazole