Antiandrogenic activity of pyrethroid pesticides and their metabolite in reporter gene assay.
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.
Sun
Hong
H
Department of Public Health, Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, Jiangsu, PR China.
Xu
Xiao-Lin
XL
Xu
Li-Chun
LC
Song
Ling
L
Hong
Xia
X
Chen
Jian-Feng
JF
Cui
Lun-Biao
LB
Wang
Xin-Ru
XR
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
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