Influence of divalent metal ions on E2-induced ER pathway in goldfish (Carassius auratus) hepatocytes

Metal ions existing in the environment could influence the estrogen pathway in aquatic animal, but the detailed mechanism is still delusive. We here showed that in male Carassius auratus hepatocytes, copper (Cu) or cadmium (Cd), did not directly induce vitellogenin (VTG) expression. Interestingly, co-exposure with Cd2+ (or Cu2+) and 17-β-estradiol (E2) greatly increased the VTG level, comparing with single treatment of E2. Meanwhile, Cd2+ or Cu2+ (but not E2) triggers HSP70 expression. But, mixture of Cd2+ or Cu2+ with E2 did not obviously raise HSP70 level. E2 also had no obvious effect on reactive oxygen species. Co-treatment of Cd2+ and E2 showed no obvious increase compared to single treatment with Cd2+. We further assume that Cd2+-involved oxidative stress generates misfolded proteins, resulting in the competition of HSP70 proteins from a heterocomplex (with estrogen receptor). Thus, dissociation of the heterocomplex actives the receptor–ligand binding activity and promotes the E2-induced VTG expression.

► Cadmium and copper did not induce the expression of vitellogenin.
► Co-treatment of (or Cu2+) and E2 increases the induction of vitellogenin compared to that with E2 alone.
► Divalent metal ions like Cd2+ influence the estrogen pathway via ROS and HSP70 in the presence of ligand (E2).