title: Endocrine disrupting effects of zearalenone, alpha- and beta-zearalenol at the level of nuclear receptor binding and steroidogenesis.
abstract: The mycotoxin zearalenone (ZEN) is a secondary metabolite of fungi which is produced by certain species of the genus Fusarium and can occur in cereals and other plant products. Reporter gene assays incorporating natural steroid receptors and the H295R steroidogenesis assay have been implemented to assess the endocrine disrupting activity of ZEN and its metabolites α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL). α-ZOL exhibited the strongest estrogenic potency (EC(50) 0.022±0.001 nM), slightly less potent than 17-β estradiol (EC(50) 0.015±0.002 nM). ZEN was ~70 times less potent than α-ZOL and twice as potent as β-ZOL. Binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of ZEN, α-ZOL or β-ZOL. ZEN, α-ZOL or β-ZOL increased production of progesterone, estradiol, testosterone and cortisol hormones in the H295R steroidogenesis assay, with peak productions at 10 μM. At 100 μM, cell viability decreased and levels of hormones were significantly reduced except for progesterone. β-ZOL increased estradiol concentrations more than α-ZOL or ZEN, with a maximum effect at 10 μM, with β-ZOL (562±59 pg/ml)>α-ZOL (494±60 pg/ml)>ZEN (375±43 pg/ml). The results indicate that ZEN and its metabolites can act as potential endocrine disruptors at the level of nuclear receptor signalling and by altering hormone production.
authors.affiliation: Institute of Agri-food and Land Use, School of Biological Sciences, Queen's University Belfast, Northern Ireland.
authors.forename: C
authors.initials: C
authors.lastname: Frizzell
authors.forename: D
authors.initials: D
authors.lastname: Ndossi
authors.forename: S
authors.initials: S
authors.lastname: Verhaegen
authors.forename: E
authors.initials: E
authors.lastname: Dahl
authors.forename: G
authors.initials: G
authors.lastname: Eriksen
authors.forename: M
authors.initials: M
authors.lastname: Sørlie
authors.forename: E
authors.initials: E
authors.lastname: Ropstad
authors.forename: M
authors.initials: M
authors.lastname: Muller
authors.forename: C T
authors.initials: CT
authors.lastname: Elliott
authors.forename: L
authors.initials: L
authors.lastname: Connolly
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D052244:Endocrine Disruptors / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D017930:Genes, Reporter / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D007536:Isomerism; D009994:Osmolar Concentration; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011987:Receptors, Steroid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D015025:Zearalenone / Q000378:metabolism / Q000633:toxicity*; D015029:Zeranol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity
chemical_list: D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D012739:Gonadal Steroid Hormones; D011987:Receptors, Steroid; C029659:zearalenol; D015025:Zearalenone; D015029:Zeranol; D006854:Hydrocortisone