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Schriks, M. et al.

Schriks, Vrabie, Gutleb, Faassen, Rietjens, Murk,

T-screen to quantify functional potentiating, antagonistic and thyroid hormone-like activities of poly halogenated aromatic hydrocarbons (PHAHs).

The present study investigates chemical thyroid hormone disruption at the level of thyroid hormone receptor ( TR) functioning. To this end the (ant)agonistic action of a series of xenobiotics was tested in the newly developed T-screen. This assay makes use of a GH(3) rat pituitary cell line, that specifically proliferates when exposed to 3,3',5-triiodo-l-thyronine (T(3)). The growth stimulatory effect is mediated via T(3)-receptors. (Ant)agonistic and potentiating action of compounds was studied in absence and presence of T(3) at its EC(50) level (0.25nM). The compounds tested included the specific TR-antagonist amiodarone, as well as a series of brominated diphenyl ethers (BDEs), including specifically synthesized BDEs with a structural resemblance to 3,5-diiodo-l-thyronine (T(2)), T(3) and T(4) (3,3',5,5'-tetraiodo-l-thyronine). The results obtained reveal that only BDE206 and amiodarone are specific antagonists. Interestingly some compounds which did not respond in the T-screen in absence of T(3), potentiated effects when tested in combination with T(3). This points at possibilities for disruption at the TR in vivo, where exposure generally occurs in presence of T(3). Altogether the results of the present study show that the newly developed T-screen can be used as a valuable tool for identification and quantification of compounds active in disturbing thyroid hormone homeostasis at the level of TR-functioning.[1]

References

T-screen to quantify functional potentiating, antagonistic and thyroid hormone-like activities of poly halogenated aromatic hydrocarbons (PHAHs). Schriks, M., Vrabie, C.M., Gutleb, A.C., Faassen, E.J., Rietjens, I.M., Murk, A.J. Toxicology in vitro : an international journal published in association with BIBRA. (2006) [Pubmed]

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