title: Fish model for assessing the in vivo estrogenic potency of the mycotoxin zearalenone and its metabolites.
abstract: The in vivo estrogenic potency of zearalenone (ZEA), a mycotoxin produced by different strains of Fusarium fungi, and its metabolites (alpha- and beta-zearalenol), have been studied in fish. Estrogenicity was evaluated using an in vitro competitive receptor binding assay and in vivo induction of vitellogenesis and zonagenesis, two estrogen receptor (ER)-mediated responses that are integral aspects of fish oogenesis. The ER binding affinities of alpha-zearalenol and ZEA in rainbow trout (Oncorhynchus mykiss) were approximately 1/150 and 1/300 to that of estradiol, respectively. Juvenile salmon (Salmo salar) were exposed to a single intraperitoneal injection of ZEA, alpha-zearalenol and beta-zearalenol (each at 1 and 10 mg/kg) and compared to fish injected with estradiol-17 beta (E2; 5 mg/kg) and controls. Using indirect enzyme-linked immunosorbent assay (ELISA) with homologous antibodies, a dose-dependent induction of vitellogenin (Vtg) and eggshell zona radiata proteins (Zr-proteins) were observed 7 days after exposure to ZEA and alpha-zearalenol. beta-Zearalenol did not elevate plasma Vtg levels, but a non-significant elevation of plasma Zr-proteins levels was observed at the highest dose (10 mg/kg). Generally, alpha-zearalenol and ZEA possess estrogenic potencies that are approximately 50% compared to that of E2, and their order of estrogenic potency (in both in vitro receptor competitive binding and in vivo induction of Vtg and Zr-proteins levels) is: alpha-zearalenol > ZEA > beta-zearalenol. Our results show that blood plasma analysis of Vtg and Zr-proteins levels provides a suitable in vivo fish model for assessing the estrogenic potencies of ZEA and its metabolites.
authors.affiliation: Department of Molecular Biology, University of Bergen, Norway. augustine.arukwe@mbi.uib.no
authors.forename: A
authors.initials: A
authors.lastname: Arukwe
authors.forename: T
authors.initials: T
authors.lastname: Grotmol
authors.forename: T B
authors.initials: TB
authors.lastname: Haugen
authors.forename: F R
authors.initials: FR
authors.lastname: Knudsen
authors.forename: A
authors.initials: A
authors.lastname: Goksøyr
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D004527:Egg Proteins / Q000096:biosynthesis; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D017686:Oncorhynchus mykiss; D009866:Oogenesis / Q000187:drug effects; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D020317:Salmo salar; D014819:Vitellogenins / Q000096:biosynthesis; D015025:Zearalenone / Q000378:metabolism / Q000494:pharmacology*; D015029:Zeranol / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004527:Egg Proteins; D004968:Estrogens, Non-Steroidal; D011960:Receptors, Estrogen; D014819:Vitellogenins; C029659:zearalenol; D004958:Estradiol; D015025:Zearalenone; D015029:Zeranol