title: Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist.
abstract: The increase in the number of reports of abnormalities in male sex development in wildlife and humans coincided with the introduction of 'oestrogenic' chemicals such as DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) into the environment. Although these phenotypic alterations are thought to be mediated by the oestrogen receptor, they are also consistent with inhibition of androgen receptor-mediated events. Here we report that the major and persistent DDT metabolite, p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), has little ability to bind the oestrogen receptor, but inhibits androgen binding to the androgen receptor, androgen-induced transcriptional activity, and androgen action in developing, pubertal and adult male rats. The results suggest that abnormalities in male sex development induced by p,p'-DDE and related environmental chemicals may be mediated at the level of the androgen receptor.
authors.affiliation: Reproductive Toxicology Branch, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Kelce
authors.forename: C R
authors.initials: CR
authors.lastname: Stone
authors.forename: S C
authors.initials: SC
authors.lastname: Laws
authors.forename: L E
authors.initials: LE
authors.lastname: Gray
authors.forename: J A
authors.initials: JA
authors.lastname: Kemppainen
authors.forename: E M
authors.initials: EM
authors.lastname: Wilson
mesh_terms: D000726:Androgen Antagonists / Q000633:toxicity*; D059002:Androgen Receptor Antagonists; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D003634:DDT / Q000378:metabolism; D003633:Dichlorodiphenyl Dichloroethylene / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D017930:Genes, Reporter; D000882:Haplorhini; D006801:Humans; D008297:Male; D015394:Molecular Structure; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D012741:Sexual Maturation / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D011960:Receptors, Estrogen; D003633:Dichlorodiphenyl Dichloroethylene; D003634:DDT