The dioxin and peroxisome proliferator-activated receptors: nuclear receptors in search of endogenous ligands

Dioxins and peroxisome proliferators represent two diverse classes of xenobiotic compounds that induce transcription of specific genes encoding cytochrome P-450 drug-metabolizing enzymes. Signal transduction by these chemicals is mediated by two distinct nuclear receptors, one of which has recently been demonstrated to be a member of the steroid hormone receptor superfamily of ligand-activated transcription factors. However, no endogenous ligand has so far been identified for either of these nuclear receptors. Lorenz Poellinger, Martin Göttlicher and Jan-Åke Gustafsson review properties of both these xenobiotic receptor systems and discuss how the molecular details in the receptor activation pathways compare with those of nuclear hormone receptors.