In vivo xenoestrogenic actions of cadmium and arsenic in anterior pituitary and uterus

Abstract

Cadmium (Cd) and arsenic (iAs) are toxic metals ubiquitously present in the environment. Both pollutants exert nonmonotonic dose-responses, being mostly cytotoxic at high concentrations but mimicking estrogen (E2) effects at low doses. Xenoestrogenic activity of Cd and iAs have been demonstrated in different hormone-dependent tumour cell lines, however, their actions in vivo remain largely unknown. Here, we investigated whether in vivo administration of low doses of Cd and iAs through drinking water would display xenoestrogenic effects in anterior pituitary gland and uterus from ovariectomized rats. 1 ppm Cd and 0.1 ppm iAs exposure increased anterior pituitary gland and uterus wet weight and induced proestrus- and estrus-like vaginal smears. Both metals stimulate cell proliferation of these tissues as they increased proliferation markers expression. More importantly, they augmented soluble guanylyl cyclase α1 subunit expression, which has been linked to hormone-dependent tumor progression. Also, Cd and iAs modified protein levels of full-length ERα and its truncated variants in an E2-like manner. Anterior pituitary hormone secretion was differentially affected by both metals. LH synthesis and release were strongly diminished after Cd exposure, and only mildly reduced by iAs. Both metals were able to increase prolactin synthesis although only iAs augmented serum prolactin levels.This study shows for the first time that Cd and iAs at low doses exert strong xenoestrogenic effects on anterior pituitary gland. The differences between Cd and iAs E2-like behaviour indicate that other Cd- and iAs-specific mechanisms could be involved. Altogether, these results contribute to knowledge of reproductive disorders associated with Cd and iAs environmental contamination.