Disruptive effects of two organotin pesticides on the thyroid signaling pathway in Xenopus laevis during metamorphosis.

Organotin compounds are the ubiquitous environmental pollutants due to their wide industrial and agricultural applications and unexpected releasing into the environment, which show characteristic of endocrine disruptors to interfere with the synthesis, receptor binding or action of endogenous-hormones. Organotin pesticides (OTPs) are used in agriculture and may impact endocrine functions on organisms. Thyroid hormones (THs) play fundamental roles in regulating the basal metabolism and energy balance, while thyroid function can be impaired by environmental contaminants. Therefore, it is crucial to clarify the effects and mechanisms of OTPs on hypothalamus-pituitary-thyroid (HPT) axis. In this study, Xenopus laevis tadpoles at stage 51 were exposed to fentin hydroxide and fenbutatin oxide (0.04, 0.20 and 1.00 µg·L-1) for 21 days. It was found that both compounds caused inhibitory effects on metamorphic development of tadpoles (e.g., significant decrease in hindlimb length and retarding development). Triiodothyronine (T3) significantly decreased in tadpoles exposed to 0.20 µg/L and 1.00 µg/L of the two OTPs for 14 days or 21 days. The expressions of TH responsive genes trß, bteb and dio2 were down-regulated, while tshß and slc5a5 were up-regulated. Surface plasmon resonance (SPR) binding assays showed that fentin hydroxide had a moderate affinity to recombinant human thyroid hormone receptor ß but fenbutatin oxide did not have. Result of the SPR assay was highly consistent with the luciferase reporter gene assays that fentin hydroxide suppressed the relative luciferase activity in the presence of T3 while fenbutatin oxide did not, demonstrating fentin hydroxide but not fenbutatin oxide displayed an antagonistic activity against T3-TR complex mediated transcriptional activation. Overall, the findings elucidated the mechanisms induced by OTPs along HPT axis. These results highlighted the adverse influences of organotin pesticides on thyroid hormone- dependent development in vertebrates and the need for more comprehensive investigations of their potential ecological risks.