Enantiomer-specific activity of o, p′-DDT with the human estrogen receptor

Abstract

There is a growing concern that environmental xenobiotics may be affecting human and wildlife health by disrupting normal endocrine function via interaction with steroid hormone receptors. Several of these persistent contaminants are chiral and may have enantiomer-specific biological properties. Previous experiments have demonstrated that (−)- o,p′-DDT enantiomer is a more active estrogen-mimic than the (+)-enantiomer in rats. However, these results have not been extrapolated to other biological systems. This study used a yeast-based assay to assess the enantiomer-specific transcriptional activity of DDT with the human estrogen receptor (hER). (+)-17β-estradiol, racemic DDT and individual DDT enantiomers were added to yeast cultures and hER activity was measured by quantification of β-galactosidase. The relative activity of o,p′ -DDT was weak compared to estradiol. For o,p′-DDT, the (−)-enantiomer was the active estrogen mimic whereas the hER activity of (+)- o,p′-DDT was negligible. The presence of the (+)-enantiomer at relatively greater concentration decreased the transcriptional activity of (−)- o,p′-DDT. This data demonstrates the need to consider stereochemistry of environmental contaminants and their potential influence on biological responses.