CYTOSOLIC RECEPTOR FOR 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN - EVIDENCE FOR A HOMOLOGOUS NATURE AMONG VARIOUS MAMMALIAN-SPECIES

Abstract

The presence and properties of the Ah receptor were examined in the guinea pig, rat, hamster, monkey and 3 different strains of mice. These species and strains have demonstrated differences in sensitivity and variability of response to 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. All species examined, with the exception of DBA/2J mice, possess similar amounts of binding protein with high affinity for 2,3,7,8-tetrachlorodibenzo-p-dioxin in hepatic tissue. Numerous dibenzo-p-dioxin congeners and polycyclic aromatic hydrocarbons demonstrated a similar rank order ability to bind to receptor molecules from these species. When analyzed by gel-exclusion high-performance liquid chromatography, hepatic cytosolic receptors from all species eluted at volumes corresponding to a similar MW range. Association of the hepatic Ah receptor with the nuclear fraction was observed in all cases following the i.p. treatment of guinea pig, rat, C57BL/6J mouse or hamster with [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin. In all species and tissues examined, with the exception of hamster duodenum and thymus, the highest concentrations of receptor were localized in the liver, lung, thymus, intestine and kidney. Exceptionally high concentrations of receptors were also observed in guinea pig testes. Despite species and tissue specific differences in the biochemical and toxicological responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds, a number of different mammalian species evidently possess Ah receptors with similar properties. The correlative differences between certain strains of mice in terms of altered specific binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin and sensitivity to this compound may be unique and not necessarily applicable to other species. Although all data indicate that the receptor mediates these responses, it appears that species- and tissue-specific differences may be determined by a number of additional factors. These results also suggest the conservation of some, as yet unknown, functional role of the receptor molecule.