title: Endocrine disrupting effects of ochratoxin A at the level of nuclear receptor activation and steroidogenesis.
abstract: Ochratoxin A (OTA) is a mycotoxin and extrolite of fungi which has been reported in a range of foods. This study uses mammalian reporter gene assays (RGAs) with natural steroid receptors and the H295R steroidogenesis assay to assess the endocrine disrupting activity of OTA. At the receptor level, OTA (within a concentration range of 0.25-2500 ng/ml) did not induce an agonistic response in an oestrogen, androgen, progestagen or glucocorticoid RGA. An antagonistic effect was observed in all of the RGAs at the highest concentration tested (2500 ng/ml). However, while there was no significant cytotoxic effect observed in the MTT (thiazolyl blue tetrazolium bromide) cell viability assay at this concentration, there was a corresponding change in cell morphology which may be related to the resulting antagonistic effect. At the hormone production level, H295R cells were used as a steroidogenesis model and exposed to OTA (within a concentration range of 0.1-1000 ng/ml). Treatment of the cells with 1000 ng/ml OTA increased the production of estradiol (117±14 ng/ml) over 3 times that of the solvent control (36±9 pg/ml). Western blotting confirmed an increase in aromatase protein. Overall the results indicate that OTA does not appear to interact with steroid receptors but has the potential to cause endocrine disruption by interfering with steroidogenesis. This is the first study identifying the effect OTA may have on production of the steroid hormone estradiol.
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Frizzell
authors.forename: S
authors.initials: S
authors.lastname: Verhaegen
authors.forename: E
authors.initials: E
authors.lastname: Ropstad
authors.forename: C T
authors.initials: CT
authors.lastname: Elliott
authors.forename: L
authors.initials: L
authors.lastname: Connolly
mesh_terms: D001141:Aromatase / Q000096:biosynthesis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000096:biosynthesis*; D017930:Genes, Reporter; D006801:Humans; D009793:Ochratoxins / Q000633:toxicity*; 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*
chemical_list: D052244:Endocrine Disruptors; D009793:Ochratoxins; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; C025589:ochratoxin A; D004958:Estradiol; D001141:Aromatase