title: Antiandrogenic activity of pyrethroid pesticides and their metabolite in reporter gene assay.
abstract: Many pesticides possess hormonal activity and have thus been classified as endocrine disruptors. Pyrethroids are commonly used pesticides worldwide, but little has been done to characterize their antiandrogenic activity potential. We tested three frequently encountered pyrethroids (fenvalerate, cypermethrin, permethrin) and their metabolite 3-phenoxybenzoic acid (3-PBA) for antiandrogenic and androgenic activity using a human androgen receptor (AR) mediated luciferase reporter gene assay in CV-1 African green monkey kidney cell. The assay displayed appropriate response to the known AR agonist 5alpha-dihydrotestosterone and AR antagonist nilutamide and flutamide. At 0.1mM, all the three tested pyrethroids significantly suppressed the luciferase expression. Further, their metabolite 3-PBA also showed antagonist activity. None of the test chemicals showed androgenic activity. Through the antiandrogenic pathways, exposure to certain pyrethroids may contribute to the damage of reproductive system. In conclusion, pyrethroid pesticides can act as antiandrogen in vitro, and metabolizing to 3-PBA cannot eliminate the antagonist activity. This result provides useful information for risk assessment of pyrethroid pesticides.
authors.affiliation: Department of Public Health, Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, Jiangsu, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Xu
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Xu
authors.forename: Ling
authors.initials: L
authors.lastname: Song
authors.forename: Xia
authors.initials: X
authors.lastname: Hong
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Chen
authors.forename: Lun-Biao
authors.initials: LB
authors.lastname: Cui
authors.forename: Xin-Ru
authors.initials: XR
authors.lastname: Wang
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D005485:Flutamide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D048289:Imidazolidines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D026023:Permethrin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010575:Pesticides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011722:Pyrethrins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D014162:Transfection
chemical_list: D000726:Androgen Antagonists; D048289:Imidazolidines; D009570:Nitriles; D010575:Pesticides; D011722:Pyrethrins; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D013196:Dihydrotestosterone; C017160:cypermethrin; D026023:Permethrin; C021277:nilutamide; D005485:Flutamide; D003907:Dexamethasone; D008156:Luciferases; C017690:fenvalerate