title: Functional associations between two estrogen receptors, environmental estrogens, and sexual disruption in the roach (Rutilus rutilus).
abstract: Wild male roach (Rutilus rutilus) living in U.K. rivers contaminated with estrogenic effluents from wastewater treatment works show feminized responses and have a reduced reproductive capability, but the chemical causation of sexual disruption in the roach has not been established. Feminized responses were induced in male roach exposed to environmentally relevant concentrations of the pharmaceutical estrogen 17alpha-ethinylestradiol, EE2 (up to 4 ng/ L), during early life (from fertilization to 84 days posthatch, dph), and these effects were signaled by altered patterns of expression of two cloned roach estrogen receptor (ER) subtypes, ERalpha. and ERbeta, in the brain and gonad/ liver. Transactivation assays were developed for both roach ER subtypes and the estrogenic potencies of steroidal estrogens differed markedly at the different ER subtypes. EE2 was by far the most potent chemical, and estrone (E1, the most prevalent environmental steroid in wastewater discharges) was equipotent with estradiol (E2) in activating the ERs. Comparison of the EC50 values for the compounds tested showed that ERbeta was 3-21-fold more sensitive to natural steroidal estrogens and 54-fold more sensitive to EE2 as compared to ERalpha. These findings add substantial support to the hypothesis that steroidal estrogens play a significant role in the induction of intersex in roach populations in U.K. rivers and that the molecular approach described could be usefully applied to understand interspecies sensitivity to xenoestrogens.
authors.affiliation: Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, 444-8787, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Katsu
authors.forename: Anke
authors.initials: A
authors.lastname: Lange
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Urushitani
authors.forename: Rie
authors.initials: R
authors.lastname: Ichikawa
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Paull
authors.forename: Laura L
authors.initials: LL
authors.lastname: Cahill
authors.forename: Susan
authors.initials: S
authors.lastname: Jobling
authors.forename: Charles R
authors.initials: CR
authors.lastname: Tyler
authors.forename: Taisen
authors.initials: T
authors.lastname: Iguchi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D003001:Cloning, Molecular; D003530:Cyprinidae / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D004963:Estrenes / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D006066:Gonads / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D046468:Sexual Development / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014819:Vitellogenins / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D004963:Estrenes; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D010636:Phenols; D012333:RNA, Messenger; D014819:Vitellogenins; C474055:octylphenol; C025256:nonylphenol