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Cross species comparisons of chemical interaction with recombinant steroid receptors in vitro.
Citation:
Wilson, V., M. Cardon, C. Rider, AND P. Hartig. Cross species comparisons of chemical interaction with recombinant steroid receptors in vitro. SETAC NA annual meeting, Vancouver, CANADA, November 09 - 13, 2014.
Impact/Purpose:
Interaction with steroid receptors is a key molecular target across vertebrates. This study uses recombinant steroid receptors to assess chemical interation with ER and AR across multiple species.
Description:
Typically, mammalian receptors are used for in vitro hazard identification and screening for endocrine disrupting compounds. There is concern, however, that differences may exist in the affinities of environmental compounds for steroid receptors from other vertebrate classes. Since interaction with steroid receptors is a key molecular target across vertebrates, our lab has developed recombinant steroid receptors for multiple vertebrate species, primarily androgen (AR) or estrogen receptors (ER), that are being used in competitive binding and/or transcriptional activation assays. Recombinant ER for nine different vertebrate species and AR for six vertebrate species, often in multiple vectors, have been developed. In vitro methods have been developed that directly compare competitive binding to the ER with the only variable within the system being the ER of the species of choice. These studies indicate that a few compounds do have higher affinities to ER from a specific species. Transcriptional activation assays with the fathead minnow AR (fhAR), supporting mechanistic information was generated indicating that bisphenol A can act as an AR antagonist in fish, consistent with morphological changes seen in the fish following in vivo exposures. Further, differences in spironolactone interaction with the fhAR versus human AR have been demonstrated as well as activation of fhAR by progestins. Overall these approaches can identify chemicals of concern for further testing and highlight potentially sensitive species. Disclaimer: This abstract does not necessarily reflect U.S. EPA policy.