Ligand-independent androgen receptor antagonism caused by the newly developed pesticide pyrifluquinazon (PFQ)

Androgen receptor (AR) is an essential component to activate AR dependent gene transcriptions. Despite wide acceptance of pharmacological controls on transcriptional pathway depending on competitive inhibitions of ligand binding, only a few examples, AR antagonism via ligand-independent mechanisms, have been recognized. Pyrifluquinazon(PFQ), a newly developed pesticide, induced representative AR antagonism against rats in in vivo and in vitro. Intriguingly, this AR antagonism was not based on inhibition of ligand binding. Instead, the evidence suggested that the AR antagonism was induced as a consequence of decline of cellular AR protein level. This study demonstrated that AR N-terminal region could be an essential element for a ligand-independent mechanism underling the AR antagonism by PFQ. Our findings should provide a novel insight into the regulation of AR-mediated transcription.

► AR antagonism caused by PFQ, a newly developed insecticide, was investigated.
► The AR antagonism caused by PFQ was mediated via a ligand-independent mechanism.
► The declining in intracellular AR level was essential for the AR antagonism by PFQ.