Study of the pregnane X receptor in the non-mammalian vertebrate species Danio rerio: polychlorinated biphenyl activation and cytochrome P450 regulation

Abstract

The pregnane X receptor (PXR) is a nuclear receptor transcription factor that regulates genes primarily involved in xenobiotic and endogenous chemical disposition and metabolism. A cluster of cytochrome P450 (CYP) genes involved in phase I metabolism are regulated by mammalian PXR. These genes can be broken down into families based on function, with CYP gene families 1-3 acting primarily in metabolism of drugs and xenobiotics such as polychlorinated biphenyls (PCBs). PCBs are a group of highly toxic, synthetic organic chemical compounds ubiquitously distributed with two major classifications: Coplanar PCBs are agonists to the aryl hydrocarbon receptor (AhR), while non coplanar PCBs are thought to act as ligands for members of the nuclear receptor transcription factor family. PCB153 has been shown to activate certain PXR target genes in mammalian cell lines, and PCB126 has been shown to induce expression of target genes under PXR regulation in vivo in zebrafish (Danio rerio). However, the pathway between PXR and its putative activators and target genes is poorly understood in non-mammalian vertebrate species. As such, we used zebrafish to investigate PXR function.