Transcriptional activation of the human estrogen receptor by DDT isomers and metabolites in yeast and MCF-7 cells.

摘要: Abstract In this study, we determined whether the DDT isomers p , ′-DUT [1,1,1,-trichloro-2,2-bis( -chlorophenyl) ethane], o ′-DDT [l,l,l-trichloro-2( -chlorophenyl)-2-( and their metabolites ′-DDD [l,l-dichloro-2,2-bis ( [1,1-dichloro-2-( -chlorophenyl)ethane], ′-DDE [1,1,-dichloro-2,2-bis( -chlorophenyl)ethylene], ′- DDE [1,1-dichloro2-( P ′-DDA [2,2-bis( -chlorophenyl)acetic acid], could bind to transcriptionally activate human estrogen receptor (hER). Novel results from competitive binding assays showed that ′-DDD, ′-DDE, ′-DDT, as well established environmental were able specifically hER with approximately 1000-fold weaker affinities for than of estradiol. contrast, only ,p′-DDT, but not ′-DUT, bound rat receptor. Moreover, two yeast expression-reporter systems, constructed test if hER, demonstrated an ,p′-DDT metabolite transactivate or LexA-hER fusion protein just a 140- 300-fold potency The in vitro triggered receptor-mediated transcription lacZ reporter gene systems. Furthermore, transactivated elicited additive response when given together systems also stimulated estrogenic endpoints estrogen-responsive MCF-7 cells: induction progesterone down-regulation hER. Thus, cells certain act directly agonists at concentrations found tissues.