Species differences in estrogen receptors and in the response to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure

The acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibits marked interspecies variability, with the guinea-pig, rat and hamster representing the species most sensitive, intermediate and most resistant to acute toxicity. Prepubertal guinea-pigs, rats and hamsters were treated with a single intraperitoneal injection of TCDD in olive oil at doses of 4, 50 and 1500 μg/kg, respectively. These exposures were chosen to produce acute toxicity and all 3 species exhibited a decrease in the rate of body weight gain during the 7 days following TCDD exposure when compared with control (olive oil-treated) animals. On the 7th day after exposure, the density and affinity of 17β-estradiol receptors were determined in the uterus and liver of TCDD-treated and control animals. The treatment with TCDD did not alter the aflinity of the receptors in these 3 species. The density of hepatic 17β-estradiol receptors was decreased 65% in the guinea pig and 92% in the rat following exposure to TCDD. In contrast, TCDD-treated hamsters exhibited no change in the density of hepatic 17β-estradiol receptors. The uterine 17β-estradiol receptors were increased in density by TCDD treatment in the hamster and in the rat when expressed per mg protein. Uterine wet weights in the guinea-pig and rat were also significantly decreased by TCDD treatment but were not changed in the hamster. When the B_max for uterine 17β-estradiol receptors was expressed as pmol/g tissue wet weight. TCDD exposure was found to produce an 11% decrease in density in the rat, while producing a 44% increase in the hamster. In control animals, the density of uterine 17β-estradiol receptors correlated inversely with the lethal dose of TCDD in these 3 species (i.e., the guinea-pig has the lowest LD₅₀ and highest density of uterine 17β-estradiol receptors). The different responses to TCDD in the 3 species suggest that the changes in 17β-estradiol receptors may be related to species-specific toxic responses associated with TCDD exposure.