Reference : Endocrine disrupting effects of zearalenone, alpha- and beta-zearalenol at the level ...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Endocrine disrupting effects of zearalenone, alpha- and beta-zearalenol at the level of nuclear receptor binding and steroidogenesis.
Frizzell, C [> > > >]
Ndossi, D [> > > >]
Verhaegen, S [> > > >]
Dahl, E [> > > >]
Eriksen, G [> > > >]
Sorlie, M [> > > >]
Ropstad, E [> > > >]
Muller, Marc mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire]
Elliott, C T [> > > >]
Connolly, L [> > > >]
Toxicology Letters
Yes (verified by ORBi)
The Netherlands
[en] Cell Line ; Cell Survival/drug effects ; Endocrine Disruptors/chemistry/metabolism/toxicity ; Estrogens, Non-Steroidal/chemistry/metabolism/toxicity ; Genes, Reporter/drug effects ; Gonadal Steroid Hormones/metabolism ; Humans ; Hydrocortisone/metabolism ; Inhibitory Concentration 50 ; Isomerism ; Osmolar Concentration ; Promoter Regions, Genetic/drug effects ; Receptors, Steroid/agonists/antagonists & inhibitors/genetics/metabolism ; Signal Transduction/drug effects ; Transcription, Genetic/drug effects ; Zearalenone/metabolism/toxicity ; Zeranol/analogs & derivatives/chemistry/toxicity
[en] 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 alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL). alpha-ZOL exhibited the strongest estrogenic potency (EC(50) 0.022+/-0.001 nM), slightly less potent than 17-beta estradiol (EC(50) 0.015+/-0.002 nM). ZEN was ~70 times less potent than alpha-ZOL and twice as potent as beta-ZOL. Binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of ZEN, alpha-ZOL or beta-ZOL. ZEN, alpha-ZOL or beta-ZOL increased production of progesterone, estradiol, testosterone and cortisol hormones in the H295R steroidogenesis assay, with peak productions at 10 muM. At 100 muM, cell viability decreased and levels of hormones were significantly reduced except for progesterone. beta-ZOL increased estradiol concentrations more than alpha-ZOL or ZEN, with a maximum effect at 10 muM, with beta-ZOL (562+/-59 pg/ml)>alpha-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.
Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.

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