An in vitro investigation of endocrine disrupting effects of the mycotoxin alternariol
Loading...
Date
2013
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier Ltd.
Abstract
Alternariol (AOH) is a mycotoxin commonly produced by Alternaria alternata on a wide range of foods. Few
studies to date have been performed to evaluate the effects of AOH on endocrine activity. The present study
makes use of in vitro mammalian cellular based assays and gene expression to investigate the ability of AOH
to act as an endocrine disruptor by various modes of action. Reporter gene assays (RGAs), incorporating nat-
ural steroid hormone receptors for oestrogens, androgens, progestagens and glucocorticoids were used to
identify endocrine disruption at the level of nuclear receptor transcriptional activity, and the H295R steroido-
genesis assay was used to assess endocrine disruption at the level of gene expression and steroid hormone
production. AOH exhibited a weak oestrogenic response when tested in the oestrogen responsive RGA
and binding of progesterone to the progestagen receptor was shown to be synergistically increased in the
presence of AOH. H295R cells when exposed to 0.1–1000 ng/ml AOH, did not cause a significant change in
testosterone and cortisol hormones but exposure to 1000 ng/ml (3.87 μM) AOH resulted in a significant in-
crease in estradiol and progesterone production. In the gene expression study following exposure to
1000 ng/ml (3.87 μM) AOH, only one gene NR0B1 was down-regulated, whereas expression of mRNA for
CYP1A1, MC2R, HSD3B2, CYP17, CYP21, CYP11B2 and CYP19 was up-regulated. Expression of the other genes
investigated did not change significantly. In conclusion AOH is a weak oestrogenic mycotoxin that also has
the ability to interfere with the steroidogenesis pathway.
Description
Toxicology and Applied Pharmacology 271 (2013) pp, 64–71
Keywords
Mycotoxin, Alternariol, Gene expression, H295R, Reporter gene assay, Steroidogenesis