title: Ligand-independent androgen receptor antagonism caused by the newly developed pesticide pyrifluquinazon (PFQ).
abstract: 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.
authors.affiliation: Research and Development Division, Nihon Nohyaku Co. Ltd., 345 Oyamada-cho, Kawachi-nagano, Osaka, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yasunaga
authors.forename: Junko
authors.initials: J
authors.lastname: Ikuta
authors.forename: Yohei
authors.initials: Y
authors.lastname: Murata
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Inoue
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Koga
authors.forename: Takao
authors.initials: T
authors.lastname: Masaki
authors.forename: Hiroto
authors.initials: H
authors.lastname: Tamura
mesh_terms: D059002:Androgen Receptor Antagonists / Q000633:toxicity*; D000818:Animals; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010575:Pesticides / Q000633:toxicity*; D011467:Prostate / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D052999:Quinazolinones / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D005466:Fluorocarbons
chemical_list: D059002:Androgen Receptor Antagonists; D008024:Ligands; D010575:Pesticides; D052999:Quinazolinones; D012333:RNA, Messenger; D011944:Receptors, Androgen; C581681:1,1,3,4-tetrahydro-6-(1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl)quinazolin-2,4-dione; D005466:Fluorocarbons