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 Cd 2+ (or Cu 2+ ) and 17-β-estradiol (E2) greatly increased the VTG level, comparing with single treatment of E2. Meanwhile, Cd 2+ or Cu 2+ (but not E2) triggers HSP70 expression. But, mixture of Cd 2+ or Cu 2+ with E2 did not obviously raise HSP70 level. E2 also had no obvious effect on reactive oxygen species. Co-treatment of Cd 2+ and E2 showed no obvious increase compared to single treatment with Cd 2+ . We further assume that Cd 2+ -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.