The metallohormone cadmium modulates AhR-associated gene expression in the small intestine of rats similar to ethinyl-estradiol

摘要: Cadmium (Cd) affects the expression of estrogen receptor (ER) and aryl hydrocarbon (AhR)-associated genes in rat uterus elicits estrogen-like activity vitro. The small intestine is highly exposed to dietary Cd which may mimic or antagonize action this tissue. We investigated effects 17-alpha-ethinylestradiol (EE2) on AhR-associated gene after oral exposure ovariectomized female Wistar rats, metallothionein (Mt1a) as a typical metal-response marker. Mt1a was strongly induced by co-treatment with CdCl2 at 2 mg/kg b.wt (Cd 2) 0.1 mg/kg EE2 than single compound (3-day gavage). 2-induced down-regulation Cyp1a1, Gsta2, Nqo1 mRNA not antagonized pure anti-estrogen (2.5 mg/kg ZK191703 s.c., ZK). Interestingly, EE2-induced 2 vivo colon cancer cell lines (HT-29 CaCo-2, treated 5 days 1 µM and/or E2 0.01 µM) low no ER-beta expression. Dose dependency studied drinking water (5 50 ppm equivalent 0.4 4 mg/kg b.wt; 0.4, 4) for 28 reference. Intestinal dose dependently induced, while AhR target were down-regulated similar more pronounced 4. propose that modulates intestinal estrogens, but (contrary its uterus) via ER-independent ER-beta-mediated mechanisms. Our new data suggest interference signaling intestine.