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 micrograms/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 17 beta-estradiol receptors were determined in the uterus and liver of TCDD-treated and control animals. The treatment with TCDD did not alter the affinity of the receptors in these 3 species. The density of hepatic 17 beta-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 17 beta-estradiol receptors. The uterine 17 beta-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 Bmax for uterine 17 beta-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 17 beta-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 17 beta-estradiol receptors). The different responses to TCDD in the 3 species suggest that the changes in 17 beta-estradiol receptors may be related to species-specific toxic responses associated with TCDD exposure.
Abbott Laboratories, IL 60064.
R E
RE
Hruska
J R
JR
Olson
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006224:Cricetinae; D004147:Dioxins / Q000633:toxicity*; D005260:Female; D006168:Guinea Pigs; D008099:Liver / Q000032:analysis / Q000187:drug effects; D008647:Mesocricetus; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000032:analysis / Q000187:drug effects*; D013045:Species Specificity; D014599:Uterus / Q000032:analysis / Q000187:drug effects
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D011960:Receptors, Estrogen