Nature 375, 581 - 585 (15 June 1995); doi:10.1038/375581a0

Persistent DDT metabolite p,p'–DDE is a potent androgen receptor antagonist

William R. Kelce^*, Christy R. Stone^*, Susan C. Laws^*, L. Earl Gray^*, Jon A. Kemppainen^† & Elizabeth M. Wilson^†‡

^*Reproductive Toxicology Branch, Developmental Toxicology Division, Health Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
The Laboratories for ^†Reproductive Biology and the Departments of Pediatrics, and ^‡Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA

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 (l,l-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.

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