Comparison of relative binding affinities to fish and mammalian estrogen receptors: the regulatory implications.
Screening and testing of chemicals binding to estrogen receptors (ERs) emerge as an important issue in several regulatory programs or frameworks. Discrepancies exist, however, whether fish ERs should be included in the regulatory programs. In view of the differences in binding affinities to ERalpha and ERbeta and the significant contribution of ERbeta to biological effects of chemicals, it remains unknown whether both types of ERs are needed for the regulatory purposes. This study collected publications on binding affinities to both mammalian and fish ERs for 65 chemicals, covering a wide range of strong, moderate, weak and non-ER binders. Systematic evaluation of the data was performed in order to compare the difference in binding affinity of chemicals to fish and mammalian ERs and to subtypes of ERs. Except the reference estrogen 17beta-estradiol, all 64 chemicals have differential values of relative binding affinity (RBA), which result mostly from the inter-laboratory tests other than interspecies differences. It is concluded that ER binding in one vertebrate species or one subtype of ERs could be extrapolated to other species or subtypes of ERs for most of chemicals for the regulatory purpose. Fish ERs are likely more sensitive to some chemicals of weak binders than mammalian ERs, suggesting the importance of including fish ERs in the regulatory programs. Issues on data interpretation and testing strategy for the regulatory purpose have been discussed.
Dang
ZhiChao
Z
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. zhichao.dang@rivm.nl
D000818:Animals; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000187:drug effects / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005399:Fishes / Q000378:metabolism*; D033161:Government Regulation; D008322:Mammals / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D013045:Species Specificity
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen