Tollefsen K-E, Mathisen R, Stenersen J
Toxicological Laboratory, Division of Molecular Cell Biology, Department of Biology, University of Oslo, Blindern, N-0316 Oslo, Norway.
Gen Comp Endocrinol. 2002 Mar;126(1):14-22. doi: 10.1006/gcen.2001.7743.
A variety of organic chemicals 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 (Oncorhunchus mykiss) were partly characterized, and the ligand-binding preference for a range of endogenous steroids and environmental estrogens (estrogen mimics) was determined 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-[(3)H]estradiol ([(3)H]-E2) with high affinity and low capacity (K(d) = 2.5-4.4 nM and B(max) = 27-97 fmol/mg protein). The Atlantic salmon ER (asER) and rainbow trout ER (rtER) exhibit similar [(3)H]-E2 binding characteristics, although livers from female fish contained a two to three times higher amounts of ER than the males in the two species. In competition studies with [(3)H]-E2, the asER and rtER were found to bind both native steroids (E2 > estrone > 17 beta-estradiol 17-glucuronide >> 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.
多种有机化学物质已被证明可与雌激素受体（ER）结合并激活该受体，进而在不同动物中引发雌激素效应。尽管ER的功能在脊椎动物中似乎具有系统发育保守性，但已证明ER结构存在相当大的种间差异。在本研究中，对大西洋鲑（Salmo salar）和虹鳟（Oncorhunchus mykiss）的肝脏ER进行了部分特性分析，并通过受体-放射性配体研究确定了一系列内源性类固醇和环境雌激素（雌激素模拟物）的配体结合偏好。结果表明，大西洋鲑和虹鳟的肝脏均含有以高亲和力和低容量结合1,2,4,6,7-[(3)H]雌二醇（[(3)H]-E2）的ER（解离常数K(d)=2.5 - 4.4 nM，最大结合量B(max)=27 - 97 fmol/mg蛋白）。大西洋鲑ER（asER）和虹鳟ER（rtER）表现出相似的[(3)H]-E2结合特性，尽管在这两个物种中，雌鱼肝脏中的ER含量比雄鱼高两到三倍。在与[(3)H]-E2的竞争研究中，发现asER和rtER既能结合天然类固醇（E2＞雌酮＞17β-雌二醇17-葡萄糖醛酸苷＞睾酮和11-酮睾酮），也能结合假定的雌激素模拟物（己烯雌酚、4-羟基他莫昔芬、乙炔雌二醇＞染料木黄酮、玉米赤霉烯酮＞4-叔辛基苯酚、4-壬基苯酚和o,p'-滴滴涕）。然而，据推测可与人类ER结合并激活的农药毒杀芬和狄氏剂，对鱼类ER并未表现出显著的结合亲和力。总体而言，发现asER和rtER以相似的亲和力和特异性结合天然类固醇和雌激素模拟物。目前的结果表明，像大西洋鲑和虹鳟这样的近缘物种表现出相似的ER配体结合需求，尽管在鱼类和人类等不同物种之间可能存在ER亲和力和特异性的种间差异。
