Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
In recent years, although the dioxins emission in the environment has decreased, harmful effects induced by dioxins on human health are still great concerns since patients exposed to dioxins such as Yusho are still suffering. Aryl hydrocarbon receptor (AhR) transactivation is well known as the dioxins’ toxic pathway, whereas the AhR transactivation-independent mechanisms are also suggested. The estrogen disruptive action is known as one of the dioxin toxicities; that is adverse estrogenic/anti-estrogenic actions. However, it is unclear in which tissues dioxins exert these effects in vivo, and the extent to which AhR transactivation contributes to these mechanisms.
To solve this problem, we investigated the estrogen-related effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is the most toxic of dioxins, on whole body by using an estrogen-responsive reporter mouse that we originally generated. Whole-body in vivo imaging showed that TCDD exerts anti-estrogenic action on the central body area but estrogenic action on the head area. Moreover, in vitro luciferase assay showed that TCDD exhibits anti-estrogenic action on the liver and kidney but estrogenic action on the pituitary gland. Under the condition of exposure to TCDD inducing these effects, the induction of Cyp1a1 expression, the marker of AhR transactivation, was not detected in each tissue, suggesting that the TCDD-induced estrogen disruptive effects may be caused by AhR transactivation-independent pathways. In this symposium, the diverse disruptive actions of dioxin on estrogen signaling will be discussed.
