title: Effects of the mycotoxin patulin at the level of nuclear receptor transcriptional activity and steroidogenesis in vitro.
abstract: Patulin (PAT) is a mycotoxin produced by various species of fungi, with Penicillium expansum being the most commonly occurring. Apples and apple products are the main sources of PAT contamination. This mycotoxin has been shown to induce toxic effects in animals, a few of which include reproductive toxicity and interference with the endocrine system. Here the endocrine disrupting potential of PAT has been investigated in vitro to identify disruption at the level of oestrogen, androgen, progestagen and glucocorticoid nuclear receptor transcriptional activity, and to assess interferences in estradiol, testosterone and progesterone steroid hormone production. At the receptor level, 0.5-5000ng/ml (0.0032-32μM) PAT did not appear to induce any specific (ant) agonistic responses in reporter gene assays (RGAs); however, nuclear transcriptional activity was affected. A >6 fold increase in the glucocorticoid receptor transcriptional activity was observed following treatment with 5000ng/ml PAT in the presence of cortisol. At the hormone production level, despite cytotoxicity being observed after treatment with 5000ng/ml PAT, estradiol levels had increased >2 fold. At 500ng/ml PAT treatment, an increase in progesterone and a decrease in testosterone production were observed. The findings of this study could be considered in assessing the health risks following exposure to PAT.
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.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Elliott
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Northern Ireland, UK. Electronic address: l.connolly@qub.ac.uk.
authors.forename: Lisa
authors.initials: L
authors.lastname: Connolly
mesh_terms: D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D052244:Endocrine Disruptors / Q000494:pharmacology / Q000633:toxicity*; D004958:Estradiol / Q000096:biosynthesis*; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009183:Mycotoxins / Q000494:pharmacology / Q000633:toxicity*; D010078:Oxazines; D010365:Patulin / Q000494:pharmacology / Q000633:toxicity*; D011374:Progesterone / Q000096:biosynthesis*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D013739:Testosterone / Q000096:biosynthesis*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014158:Transcription, Genetic / Q000187:drug effects; D014966:Xanthenes
chemical_list: D052244:Endocrine Disruptors; D009183:Mycotoxins; D010078:Oxazines; D018160:Receptors, Cytoplasmic and Nuclear; D013778:Tetrazolium Salts; D013844:Thiazoles; D014966:Xanthenes; C005843:resazurin; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D010365:Patulin; C022616:thiazolyl blue
keywords: Cytotoxicity; Endocrine disruptor; H295R; Mycotoxin; Patulin; Reporter gene assay