Differential estrogen receptor binding of estrogenic substances: a species comparison
| Autor: | Timothy R. Zacharewski, Trine Celius, Robert G. Halgren, Jason Matthews |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Coumestrol
Recombinant Fusion Proteins Endocrinology Diabetes and Metabolism Molecular Sequence Data Clinical Biochemistry Phytoestrogens Biology Binding Competitive Biochemistry Mice chemistry.chemical_compound Endocrinology Estrogen Receptor Modulators Species Specificity Animals Humans Amino Acid Sequence Estrogens Non-Steroidal Cloning Molecular Receptor Molecular Biology Peptide sequence Flavonoids chemistry.chemical_classification Dieldrin Sequence Homology Amino Acid Estrogen receptor binding Estrogens Lizards Methoxychlor Cell Biology Mycotoxins Ligand (biochemistry) Genistein Isoflavones Fusion protein Amino acid Dissociation constant Receptors Estrogen chemistry Oncorhynchus mykiss Flavanones Molecular Medicine Plant Preparations Chickens |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 74:223-234 |
| ISSN: | 0960-0760 |
| DOI: | 10.1016/s0960-0760(00)00126-6 |
| Popis: | The study investigated the ability of 34 natural and synthetic chemicals to compete with [3H]17beta-estradiol (E2) for binding to bacterially expressed glutathione-S-transferase (GST)-estrogen receptors (ER) fusion proteins from five different species. Fusion proteins consisted of the ER D, E and F domains of human alpha (GST-hERalphadef), mouse alpha (GST-mERalphadef), chicken (GST-cERdef), green anole (GST-aERdef) and rainbow trout ERs (GST-rtERdef). All five fusion proteins displayed high affinity for E2 with dissociation constants (K(d)) ranging from 0.3 to 0.9 nM. Although, the fusion proteins exhibited similar binding preferences and binding affinities for many of the chemicals, several differences were observed. For example, alpha-zearalenol bound with greater affinity to GST-rtERdef than E2, which was in contrast to other GST-ERdef fusion proteins examined. Coumestrol, genistein and naringenin bound with higher affinity to the GST-aERdef, than to the other GST-ERdef fusion proteins. Many of the industrial chemicals examined preferentially bound to GST-rtERdef. Bisphenol A, 4-t-octylphenol and o,p' DDT bound with approximately a ten-fold greater affinity to GST-rtERdef than to other GST-ERdefs. Methoxychlor, p,p'-DDT, o,p'-DDE, p,p'-DDE, alpha-endosulfan and dieldrin weakly bound to the ERs from the human, mouse, chicken and green anole. In contrast, these compounds completely displaced [3H]E2 from GST-rtERdef. These results demonstrate that ERs from different species exhibit differential ligand preferences and relative binding affinities for estrogenic compounds and that these differences may be due to the variability in the amino acid sequence within their respective ER ligand binding domains. |
| Databáze: | OpenAIRE |
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