Estrogen Mimics Bind with Similar Affinity and Specificity to the Hepatic Estrogen Receptor in Atlantic Salmon (Salmo salar) and Rainbow Trout (Oncorhynchus mykis

Sammendrag

Abstract A variety of org. chems. have been documented to bind to and activate the estrogen receptor (ER) and consequently induce estrogenic effects in different animals. Although the function of the ER seems phylogenetically conserved in vertebrates, a considerable interspecies variation in the structure of the ER has been demonstrated. In this study, the hepatic ER from Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) were partly characterized, and the ligand-binding preference for a range of endogenous steroids and environmental estrogens (estrogen mimics) was detd. by receptor-radio ligand studies. The results show that both Atlantic salmon and rainbow trout livers contain ERs that bind 1,2,4,6,7-[3H]estradiol ([3H]-E2) with high affinity and low capacity (Kd = 2.5-4.4 nM and Bmax = 27-97 fmol/mg protein). The Atlantic salmon ER (asER) and rainbow trout ER (rtER) exhibit similar [3H]-E2 binding characteristics, although livers from female fish contained a two to three times higher amts. of ER than the males in the two species. In competition studies with [3H]-E2, the asER and rtER were found to bind both native steroids (E2 > estrone >17-estradiol 17-glucuronide .mchgt. testosterone and 11-ketotestosterone) and putative estrogen mimics (diethylstilbestrol, 4-hydroxytamoxifen, ethynylestradiol > genistein, zearalenone >4-t-octylphenol, 4-n-nonylphenol, and o,p'-DDT). The pesticides toxaphen and dieldrin, which are proposed to bind to and activate the human ER, did not display significant binding affinity for the fish ER, however. In general, the asER and rtER were found to bind both native steroids and estrogen mimics with similar affinity and specificity. The present results suggest that closely related species such as Atlantic salmon and rainbow trout display similar ER ligand-binding requirements, although interspecies differences in ER affinity and specificity between divergent species such as fish and humans may exist.