Disruption of thyroid hormone binding to sea bream recombinant transthyretin by ioxinyl and polybrominated diphenyl ethers.
A number of chemicals released into the environment share structural similarity to the thyroid hormones (THs), thyroxine (T(4)) and triiodothyronine (T(3)) and it is thought that they may interfere with the thyroid axis and behave as endocrine disruptors (EDs). One of the ways by which such environmental contaminants may disrupt the TH axis is by binding to TH transporter proteins. Transthyretin (TTR) is one of the thyroid hormone binding proteins responsible for TH transport in the blood. TTR forms a stable tetramer that binds both T(4) and T(3) and in fish it is principally synthesized in the liver but is also produced by the brain and intestine. In the present study, we investigate the ability of some chemicals arising from pharmaceutical, industrial or agricultural production and classified as EDs, to compete with [I(125)]-T(3) for sea bream recombinant TTR (sbrTTR). Ioxinyl, a common herbicide and several polybrominated diphenyl ethers were strong inhibitors of [I(125)]-T(3) binding to TTR and some showed even greater affinity than the natural ligand T(3). The TTR competitive binding assay developed offers a quick and effective tool for preliminary risk assessment of chemicals which may disrupt the thyroid axis in teleost fish inhabiting vulnerable aquatic environments.
Morgado
Isabel
I
Centro de Ciências do Mar, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
Hamers
Timo
T
Van der Ven
Leo
L
Power
D M
DM
D000818:Animals; D001667:Binding, Competitive; D004054:Diethylstilbestrol / Q000378:metabolism; D052244:Endocrine Disruptors / Q000378:metabolism*; D005411:Flame Retardants / Q000378:metabolism; D007462:Iodobenzenes / Q000633:toxicity; D009570:Nitriles / Q000633:toxicity; D010416:Pentachlorophenol / Q000378:metabolism; D010636:Phenols / Q000378:metabolism; D010647:Phenyl Ethers / Q000633:toxicity; D011075:Polybrominated Biphenyls / Q000633:toxicity; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D021541:Sea Bream; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism*
D052244:Endocrine Disruptors; D005411:Flame Retardants; D007462:Iodobenzenes; D009570:Nitriles; D010636:Phenols; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; D011228:Prealbumin; D011994:Recombinant Proteins; D014284:Triiodothyronine; D004054:Diethylstilbestrol; C025256:nonylphenol; C008161:ioxynil; D010416:Pentachlorophenol; D013974:Thyroxine