Nuclear receptors and susceptibility to chemical exposure in aquatic organisms

Nuclear receptors (NRs) constitute a superfamily of transcriptional factors that participate in homeostasis and development through the binding of endogenous compounds. Despite this constitutive activity, some xenobiotics can also bind to NRs and disturb some signaling pathways, giving rise to the concept that NR activity can be modulated by antagonists or competitive agonists. Some NRs, such as the Pregnane X receptor (PXR), Peroxisome Proliferator Activated Receptors (PPARs) and Constitutive Androstane Receptor (CAR) have received particular attention because after binding to xenobiotics, they activate the expression of genes involved in Phases I, II and III of biotransformation pathways. Another important protein involved in the signaling of toxic compounds is the aromatic hydrocarbon receptor (AhR), a member of the basic helix loop-helix (bHLH) PER-ARNT-SIM (PAS) family of nuclear transcription factors. AhR modulates an important panel of cognate genes and is remarkably prone to protein–protein interactions interfering with transcription factors and NRs. Several observations have been made associating the exposure to chemicals with adverse effects on reproduction of aquatic organisms, termed endocrine disrupting compounds (EDC). NRs are believed to play an essential role in the adverse effects elicited by EDC and some mechanisms are addressed in this review.