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; Elliott, C T; Connolly, L

doi:10.1016/j.toxlet.2011.07.015

Article (Scientific journals)

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

Frizzell, C; Ndossi, D; Verhaegen, S et al.

2011 • In Toxicology Letters, 206 (2), p. 210-217

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/122015

DOI
10.1016/j.toxlet.2011.07.015

PubMed
21803136

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Keywords :

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

Abstract :

[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.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Frizzell, C

Ndossi, D

Verhaegen, S

Dahl, E

Eriksen, G

Sorlie, M

Ropstad, E

Muller, Marc ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire

Elliott, C T

Connolly, L

Language :

English

Title :

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

Publication date :

2011

Journal title :

Toxicology Letters

ISSN :

0378-4274

eISSN :

1879-3169

Publisher :

Elsevier, Amsterdam, Netherlands

Volume :

206

Issue :

Pages :

210-217

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 16 May 2012

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