Endocrine disrupting effects of zearalenone, alpha- and beta-zearalenol at the level of nuclear receptor binding and steroidogenesis

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 (EC50 0.022 +/- 0.001 nM), slightly less potent than 17-beta estradiol (EC50 0.015 +/- 0.002 nM). ZEN was similar to 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 mu M. At 100 mu M, 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 mu M, with beta-ZOL (562 +/- 59 mu g/ml) > alpha-ZOL (494 +/- 60 mu pg/ml) > ZEN (375 +/- 43 mu g/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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.