Specific binding of hydroxylated polychlorinated biphenyl metabolites and other substances to bovine calf uterine estrogen receptor: structure-binding relationships.
The objectives of this research were: (1) to survey a wide variety of structurally diverse (and mostly chlorinated) aromatic chemicals for specific binding to the calf uterine estrogen receptor; (2) to develop a quantitative structure-binding relationship (QSBR) for hydroxylated polychlorinated biphenyls (OH-PCBs). This report specifically includes data on substances that did not exhibit specific binding to ER thereby exploring the structural requirements for specific binding to the estrogen receptor. Although several other QSBRs for OH-PCBs have been reported, this study presents data on a larger, environmentally relevant set of OH-PCBs than previously reported. Fifty three chemicals were tested for the ability to bind specifically to calf uterine estrogen receptor. All but three OH-PCBs bound specifically to calf uterine ER. For DDT compounds, receptor binding affinity followed the pattern: o,p'-DDT > o,p'-DDE > o,p'-DDD (Not active). Also exhibiting measurable affinity were 17 beta-estradiol (a positive control and the native ligand of the estrogen receptor), 2,4,6-trichlorobiphenyl and 4-chloro-2-isopropyl-5-methylphenol. Substances that did not bind to calf uterine estrogen receptor comprised several individual PCB congeners, chlorinated naphthalenes and naphthalenols, chlorinated bibenzyls, chlorinated phenols, and 9-chloro-retene. For 25 hydroxylated PCBs, a five parameter QSBR was developed using multiple linear regression and selection of the most parsimonius model from a total of seven molecular modeling parameters examined. The QSBR model predicted the ER binding log (IC50) to within one log unit.
Kramer
V J
VJ
Fisheries and Wildlife Department, Michigan State University, East Lansing, USA. rahvjk@rohmhaas.com
Giesy
J P
JP
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000378:metabolism* / Q000633:toxicity; D005260:Female; D066298:In Vitro Techniques; D008958:Models, Molecular; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D011960:Receptors, Estrogen / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014599:Uterus / Q000378:metabolism
D004785:Environmental Pollutants; D011960:Receptors, Estrogen; D011078:Polychlorinated Biphenyls