Ligand-independent androgen receptor antagonism caused by the newly developed pesticide pyrifluquinazon (PFQ)
| Autor: | Kazuyoshi Inoue, Hiroto Tamura, Yohei Murata, Ryoko Yasunaga, Hiroyasu Koga, Takao Masaki, Junko Ikuta |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Transcriptional Activation Transcription Genetic Pharmacology Toxicology Ligands Rats Sprague-Dawley In vivo Cell Line Tumor Androgen Receptor Antagonists Animals Humans RNA Messenger Pesticides Receptor Quinazolinones Chemistry HEK 293 cells Prostate Organ Size Ligand (biochemistry) In vitro Rats Androgen receptor HEK293 Cells Cell culture Receptors Androgen Antagonism |
| Zdroj: | Reproductive toxicology (Elmsford, N.Y.). 35 |
| ISSN: | 1873-1708 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect