title: Differing species responsiveness of estrogenic contaminants in fish is conferred by the ligand binding domain of the estrogen receptor.
abstract: Exposure to estrogenic endocrine disrupting chemicals (EDCs) induces a range of adverse effects, notably on reproduction and reproductive development. These responses are mediated via estrogen receptors (ERs). Different species of fish may show differences in their responsiveness to environmental estrogens but there is very limited understanding on the underlying mechanisms accounting for these differences. We used custom developed in vitro ERα reporter gene assays for nine fish species to analyze the ligand- and species-specificity for 12 environmental estrogens. Transcriptonal activities mediated by estradiol-17β (E2) were similar to only a 3-fold difference in ERα sensitivity between species. Diethylstilbestrol was the most potent estrogen (∼ 10-fold that of E2) in transactivating the fish ERαs, whereas equilin was about 1 order of magnitude less potent in all species compared to E2. Responses of the different fish ERαs to weaker environmental estrogens varied, and for some considerably. Medaka, stickleback, bluegill and guppy showed higher sensitivities to nonylphenol, octylphenol, bisphenol A and the DDT-metabolites compared with cyprinid ERαs. Triclosan had little or no transactivation of the fish ERαs. By constructing ERα chimeras in which the AF-containing domains were swapped between various fish species with contrasting responsiveness and subsequent exposure to different environmental estrogens. Our in vitro data indicate that the LBD plays a significant role in accounting for ligand sensitivity of ERα in different species. The differences seen in responsiveness to different estrogenic chemicals between species indicate environmental risk assessment for estrogens cannot necessarily be predicted for all fish by simply examining receptor activation for a few model fish species.
authors.affiliation: Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, and Department of Basic Biology, The Graduate School for Advanced Studies (SOKENDAI) , Okazaki, Aichi 444-8787, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Anke
authors.initials: A
authors.lastname: Lange
authors.forename: Ikumi
authors.initials: I
authors.lastname: Hirakawa
authors.forename: Saki
authors.initials: S
authors.lastname: Tohyama
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ogino
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizutani
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kagami
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Kusano
authors.forename: Masaru
authors.initials: M
authors.lastname: Ihara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Norihisa
authors.initials: N
authors.lastname: Tatarazako
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ohta
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Katsu
authors.forename: Charles R
authors.initials: CR
authors.lastname: Tyler
authors.forename: Taisen
authors.initials: T
authors.lastname: Iguchi
mesh_terms: D000818:Animals; D052244:Endocrine Disruptors / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005399:Fishes / Q000378:metabolism*; D017930:Genes, Reporter; D008024:Ligands; D017434:Protein Structure, Tertiary; D013045:Species Specificity; D015533:Transcriptional Activation / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000494:pharmacology*
chemical_list: D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D004967:Estrogens; D008024:Ligands; D014874:Water Pollutants, Chemical