Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist.
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.
Kelce
W R
WR
Reproductive Toxicology Branch, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Stone
C R
CR
Laws
S C
SC
Gray
L E
LE
Kemppainen
J A
JA
Wilson
E M
EM
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
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D011960:Receptors, Estrogen; D003633:Dichlorodiphenyl Dichloroethylene; D003634:DDT