Endosulfan modulates estrogen-dependent genes like a non-uterotrophic dose of 17β-estradiol

The estrogenic activity of environmentally relevant doses of endosulfan was investigated using an animal model. Ovariectomized adult rats were injected once a day for 3 days with sesame oil (control), 0.02 mg/kg/day 17β-estradiol (an uterotrophic dose; UE2), 0.0002 mg/kg/day 17β-estradiol (a non-uterotrophic dose; NUE2), or 0.006, 0.06, 0.6 or 6 mg/kg/day endosulfan. After 24 h of treatment, the uteri were weighed (uterotrophic assay) and the luminal epithelial cell height (LECH) and progesterone receptor (PR), and estrogen receptor alpha (ERα) protein levels were measured. PR, ERα, and complement factor-3 (C3) mRNAs were evaluated using real-time PCR. Uterine weight and LECH were only increased in UE2-treated rats. PR, ERα and C3 expression levels were modified in most of the endosulfan-treated groups, showing an identical pattern of expression to the NUE2-group. Our results show that the pesticide endosulfan mimics non-uterotrophic E2 actions, strengthening the hypothesis that endosulfan is a widespread xenoestrogen.