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STRATEGY FOR ASSESSING IMPACTS OF THYROID DISRUPTING CHEMICALS IN TELEOSTEANS Joseph G. Schnitzler, Klaren P. H. M., Celis N., Blust R., Covaci A., Dirtu A. C., Silvestre F., Das K. Endocrine disruptors synthetic chemicals mimic or block hormones disrupt hormone function Marine organisms presents high concentrations of EDCs Thyroid = targed for EDCs? Cl (Cl)n Similar chemical Cl as thyroid structures Cl hormones Cl May generate an endocrine disruption (Cl)n Cl Thyroxine Triiodothyronine DDT PCB Thyroid toxicants Generally defined as compounds that alter thyroid hormones levels 116 environmental compounds are suspected Studies often incorporate an incomplete picture of dynamic relationships within the HPT axis Important to capture indicative endpoints Current study present some methods Experimental design 5 tanks containing each 15 sea bass [7 tracer PCBs] A1254 & A1260 Day 0: 15g et 11cm Day 120: 30g et 15cm Thyroid parameters T4 T3 T4G T4S Histology Deiodination + = synthesis and conjugation secretion activity = metabolism Thyroid hormone metabolism T4 is converted to T3 by deiodination T4 is also the substrate for the phase II conjugation enzyme reactions Maglich J M et al. J. Biol. Chem. 2004;279:19832-19838 Thyroid parameters T4 T3 T4G T4S T4 and T3 Histology Deiodination + Tissue TH = synthesis and conjugation concentration secretion activity = metabolism = status T4 status * Thyroid histology Measurements: follicle size, cell heigths, roundness, form factor, aspect ratio. Follicle size heterogeneity @ 10 ppm lower number of follicles degenerated colloid enlargement of interstitial tissue disorganized tissue Follicle size heterogeneity Ultrastructure Flattened epithelial cells High epithelial cells Flattened epithelial cells High epithelial cells T3 status * * * Deiodinase activity raises * SULT activity decreases * * Effects Neither size, nor weight differences could be observed between treatment groups No decreased fitness or survival Conclusions… Environmental relevant concentrations Maintain the thyroid hormone levels in an acceptable range Conclusions… T4 + extensive autoregulatory feedback mechanisms! T3 + - Conclusions… Environmental relevant concentrations Maintain the thyroid hormone levels in an acceptable range Extensive auto-regulatory feedback mechanisms! Act at both central and peripheral levels Very efficient! No causal link to decreased fitness or survival Early development of fishes = interesting thyroid hormone effect screen? Very susceptible to thyroid disruption? Thank you for your attention!!!
