Interaction of Galaxolide (R) with the human and trout estrogen receptor-alpha
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| Authors: | Simmons, DBD; Marlatt, VL; Trudeau, VL; Sherry, JP; Metcalfe, CD |
| Year: | 2010 |
| Journal: | Science of the Total Environment 408: 6158-6164 Article Link (DOI) |
| Title: | Interaction of Galaxolide (R) with the human and trout estrogen receptor-alpha |
| Abstract: | Synthetic musks have been detected in sewage effluents surface waters and fish tissues where the polycyclic musk compound HHCB (Galaxolide (R)) is the dominant compound in those matrices In the present study the Galaxolide (R) formulation was tested in the yeast estrogenicity screening (YES) assay and also tested in in vitro and in vivo teleost systems to determine whether it interacts with the estrogen receptor as either an agonist or antagonist. In those tests Galaxolide (R) did not act as an estrogen agonist, however there was strong evidence of antagonistic activity as Galaxolide (R) inhibited the estrogenic activity of 17 beta-estradiol (E2) In the YES assay based on a recombinant strain of yeast containing the human estrogen receptor (i e hER alpha), Galaxolide (R) inhibited the effects of E2 in a dose-dependent manner (IC50 =1 63 x 10(-5) M) In a luciferase reporter gene assay based on the rainbow trout estrogen receptor e rtER) transfected into a rainbow trout gonadal (RTG-2) cell line the IC50 for the antagonistic effect of Galaxolide (R) was 2 79 x 10-9 M In an in vivo assay based on modulation of vitellogenin in rainbow trout Galaxolide (R) i p injected into trout at a dose of 3 64 mg/kg caused inhibition of E2-induced vitellogenin production That dose is within the range of concentrations of Galaxolide (R) that have been detected in tissues of fish from contaminated locations (C) 2010 Elsevier B V All rights reserved |
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