Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: a potential novel mechanism of endocrine disruption.
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Thomas P, Dong J
Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: a potential novel mechanism of endocrine disruption.
J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):175-9. Epub 2006 Nov 7.
- PubMed ID
- 17088055 [ View in PubMed]
- Abstract
A wide variety of environmental contaminants have been shown to exert estrogenic actions in wildlife and laboratory animals through binding to nuclear estrogen receptors (ERs) and subsequent transcription of estrogen responsive genes. We show here that several of these environmental estrogens also bind to the novel seven-transmembrane estrogen receptor, GPR30, to activate alternative estrogen signaling pathways in an ER-negative cell line (HEK293) stably transfected with the receptor. Genestein was the most effective competitor for the receptor (IC(50) 133 nM), with a relative binding affinity (RBA) 13% that of estradiol-17beta (E2). Bisphenol A, zearalonone, and nonylphenol also had relatively high binding affinities for GPR30 with RBAs of 2-3%. Kepone, p,p'-DDT, 2,2',5',-PCB-4-OH and o,p'-DDE had lower affinities with RBAs of 0.25-1.3%, whereas o,p'-DDT, p,p'-DDE, methoxychlor and atrazine caused less than 50% displacement of [(3)H]-E2 at concentrations up to 10 microM. Overall, the binding affinities of these compounds for GPR30 are broadly similar to their affinities to the ERs. Environmental estrogens with relatively high binding affinities for GPR30 (genestein, bisphenol A, nonylphenol and Kepone) also displayed estrogen agonist activities in an in vitro assay of membrane-bound adenylyl cyclase activity, a GPR30-dependent signaling pathway activated by estrogens. The results indicate that nontraditional estrogen actions mediated through GPR30 are potentially susceptible to disruption by a variety of environmental estrogens.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Estradiol G-protein coupled estrogen receptor 1 Protein Humans UnknownBinderDetails Estradiol acetate G-protein coupled estrogen receptor 1 Protein Humans UnknownNot Available Details Estradiol benzoate G-protein coupled estrogen receptor 1 Protein Humans UnknownNot Available Details Estradiol cypionate G-protein coupled estrogen receptor 1 Protein Humans UnknownNot Available Details Estradiol dienanthate G-protein coupled estrogen receptor 1 Protein Humans UnknownNot Available Details Estradiol valerate G-protein coupled estrogen receptor 1 Protein Humans UnknownNot Available Details Genistein G-protein coupled estrogen receptor 1 Protein Humans UnknownNot Available Details