Endocrine disrupting potential of selected azole and organophosphorus pesticide products through suppressing the dimerization of human androgen receptor in genomic pathway

Several pesticides widely used in agriculture have been considered to be endocrine disrupting chemicals through their binding affinities to estrogen or androgen receptors. This study was conducted to clarify the human androgen receptor (hAR)-mediated genomic endocrine disrupting mechanism of eight selected pesticide products by in vitro assay providing the Organization for Economic Co-operation and Development Test Guideline No. 458, 22Rv1/MMTV_GR-KO AR transcriptional activation assay and a homo-dimerization confirmation assay. None of the tested pesticide products showed an AR agonistic effect, whereas they were all determined to be AR antagonists at non-toxic concentrations. Also, the eight pesticide products were verified as true AR antagonists through a specificity control test. In the Bioluminescence Resonance Energy Transfer-based AR homo-dimerization confirmation assay, the eight pesticide products did not induce AR homo-dimerization. Addition-ally, western blotting revealed that none of the eight pesticide products induced AR translocation from the cytoplasm to the nucleus. In conclusion, we found for the first-time evidence to understand the AR-mediated endocrine disrupting mechanisms induced by selected azole and organophosphorus pesticide products.