title: An in vitro investigation of endocrine disrupting effects of the mycotoxin alternariol.
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 natural 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 steroidogenesis 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 0.1-1000ng/ml AOH, did not cause a significant change in testosterone and cortisol hormones but exposure to 1000ng/ml (3.87μM) AOH resulted in a significant increase in estradiol and progesterone production. In the gene expression study following exposure to 1000ng/ml (3.87μM) 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.
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Frizzell
authors.forename: Doreen
authors.initials: D
authors.lastname: Ndossi
authors.forename: Shewit
authors.initials: S
authors.lastname: Kalayou
authors.forename: Gunnar S
authors.initials: GS
authors.lastname: Eriksen
authors.forename: Steven
authors.initials: S
authors.lastname: Verhaegen
authors.forename: Morten
authors.initials: M
authors.lastname: Sørlie
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Elliott
authors.forename: Erik
authors.initials: E
authors.lastname: Ropstad
authors.forename: Lisa
authors.initials: L
authors.lastname: Connolly
mesh_terms: D000728:Androgens / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D004967:Estrogens / Q000378:metabolism; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000633:toxicity*; D011372:Progestins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000728:Androgens; D052244:Endocrine Disruptors; D004967:Estrogens; D005938:Glucocorticoids; D007783:Lactones; D011372:Progestins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; C005197:alternariol
keywords: Alternariol; Gene expression; H295R; Mycotoxin; Reporter gene assay; Steroidogenesis