Human Dioxin Receptor Chimera Transactivation in a Yeast Model System and Studies on Receptor Agonists and Antagonists

Abstract: A yeast dioxin receptor chimera model has been developed to study ligand binding and transactivation properties of the human dioxin receptor. Using this new yeast model, the human dioxin receptor chimera was found to possess a constitutive transactivity on a LacZ reporter gene, however, the transactivation by the chimera was enhanced by the addition of several polycyclic aromatic hydrocarbons to the culture medium. The order of best polycyclic aromatic hydrocarbon inducer to worst correlated well with the known in vitro dioxin receptor binding affinities for these polycyclic aromatic hydrocarbons. 7, 8‐Benzoflavone, a weak dioxin receptor agonist and strong antagonist of the mammalian dioxin receptor also behaved as a weak agonist and strong antagonist of the human dioxin receptor chimera expressed in yeast. The implications for these findings as well as the utility of this new yeast human dioxin receptor chimera model are discussed. 1995 Nordic Pharmacological Society