title: Evolution of estrogen receptors in ray-finned fish and their comparative responses to estrogenic substances.
abstract: In vertebrates, estrogens play fundamental roles in regulating reproductive activities through estrogen receptors (ESRs), and disruption of estrogen signaling is now of global concern for both wildlife and human health. To date, ESRs of only a limited number of species have been characterized. We investigated the functional diversity and molecular basis or ligand sensitivity of ESRs among ray-finned fish species (Actinopterygii), the most variable group within vertebrates. We cloned and characterized ESRs from several key species in the evolution of ray-finned fish including bichir (Polypteriformes, ESR1 and ESR2) at the basal lineage of ray-finned fish, and arowana (Osteoglossiformes, ESR1 and ESR2b) and eel (Anguilliformes, ESR1, ESR2a and ESR2b) both belonging to ancient early-branching lineages of teleosts, and suggest that ESR2a and ESR2b emerged through teleost-specific whole genome duplication, but an ESR1 paralogue has been lost in the early lineage of euteleost fish species. All cloned ESR isoforms showed similar responses to endogenous and synthetic steroidal estrogens, but they responded differently to non-steroidal estrogenic endocrine disrupting chemicals (EDCs) (e.g., ESR2a exhibits a weaker reporter activity compared with ESR2b). We show that variation in ligand sensitivity of ESRs can be attributed to phylogeny among species of different taxonomic groups in ray-finned fish. The molecular information provided contributes both to understanding of the comparative role of ESRs in the reproductive biology of fish and their comparative responses to EDCs.
authors.affiliation: Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan; Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Tohyama
authors.affiliation: Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan. Electronic address: miyagawa@nibb.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: University of Exeter, Biosciences, College of Life & Environmental Sciences, Exeter EX4 4QD, United Kingdom.
authors.forename: Anke
authors.initials: A
authors.lastname: Lange
authors.affiliation: Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ogino
authors.affiliation: Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizutani
authors.affiliation: Research Center for Environmental Quality Management, Kyoto University, Otsu, Shiga 520-0811, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ihara
authors.affiliation: Research Center for Environmental Quality Management, Kyoto University, Otsu, Shiga 520-0811, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Center for Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Tatarazako
authors.affiliation: Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: University of Exeter, Biosciences, College of Life & Environmental Sciences, Exeter EX4 4QD, United Kingdom.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Tyler
authors.affiliation: Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan. Electronic address: taisen@nibb.ac.jp.
authors.forename: Taisen
authors.initials: T
authors.lastname: Iguchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D003001:Cloning, Molecular; D052244:Endocrine Disruptors / Q000494:pharmacology*; D045166:Estradiol Congeners / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D019143:Evolution, Molecular; D005260:Female; D005399:Fishes; D057809:HEK293 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D010053:Ovary / Q000378:metabolism; D010802:Phylogeny; D011960:Receptors, Estrogen / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D052244:Endocrine Disruptors; D045166:Estradiol Congeners; D004967:Estrogens; D011960:Receptors, Estrogen
keywords: Endocrine disruptors; Estrogen receptor; Fish; Reporter gene assay