title: Do persistent organic pollutants interact with the stress response? Individual compounds, and their mixtures, interaction with the glucocorticoid receptor.
abstract: Persistent organic pollutants (POPs) are toxic substances, highly resistant to environmental degradation, which can bio-accumulate and have long-range atmospheric transport potential (UNEP, 2001). The majority of studies on endocrine disruption have focused on interferences on the sexual steroid hormones and so have overlooked disruption to glucocorticoid hormones. Here the endocrine disrupting potential of individual POPs and their mixtures has been investigated in vitro to identify any disruption to glucocorticoid nuclear receptor transcriptional activity. POP mixtures were screened for glucocorticoid receptor (GR) translocation using a GR redistribution assay (RA) on a CellInsight™ NXT high content screening (HCS) platform. A mammalian reporter gene assay (RGA) was then used to assess the individual POPs, and their mixtures, for effects on glucocorticoid nuclear receptor transactivation. POP mixtures did not induce GR translocation in the GR RA or produce an agonist response in the GR RGA. However, in the antagonist test, in the presence of cortisol, an individual POP, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), was found to decrease glucocorticoid nuclear receptor transcriptional activity to 72.5% (in comparison to the positive cortisol control). Enhanced nuclear transcriptional activity, in the presence of cortisol, was evident for the two lowest concentrations of perfluorodecanoic acid (PFOS) potassium salt (0.0147mg/ml and 0.0294mg/ml), the two highest concentrations of perfluorodecanoic acid (PFDA) (0.0025mg/ml and 0.005mg/ml) and the highest concentration of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) (0.0000858mg/ml). It is important to gain a better understanding of how POPs can interact with GRs as the disruption of glucocorticoid action is thought to contribute to complex diseases.
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
authors.forename: Jodie
authors.initials: J
authors.lastname: Wilson
authors.affiliation: Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: Hanne Friis
authors.initials: HF
authors.lastname: Berntsen
authors.affiliation: Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: Karin Elisabeth
authors.initials: KE
authors.lastname: Zimmer
authors.affiliation: Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: Steven
authors.initials: S
authors.lastname: Verhaegen
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Frizzell
authors.affiliation: Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Ropstad
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Northern Ireland, United Kingdom. Electronic address: l.connolly@qub.ac.uk.
authors.forename: Lisa
authors.initials: L
authors.lastname: Connolly
mesh_terms: D002460:Cell Line; D003652:Decanoic Acids / Q000633:toxicity; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity; D004347:Drug Interactions; D052244:Endocrine Disruptors / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D005466:Fluorocarbons / Q000633:toxicity; D017930:Genes, Reporter / Q000187:drug effects; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity; D006801:Humans; D007306:Insecticides / Q000633:toxicity; D010573:Pesticide Residues / Q000633:toxicity; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D003652:Decanoic Acids; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D005466:Fluorocarbons; D055768:Halogenated Diphenyl Ethers; D007306:Insecticides; D010573:Pesticide Residues; D011965:Receptors, Glucocorticoid; C511295:2,2',4,4'-tetrabromodiphenyl ether; C036567:perfluorodecanoic acid; D003633:Dichlorodiphenyl Dichloroethylene
keywords: Glucocorticoid receptor; High content analysis; Mixtures; Persistent organic pollutants; Reporter gene assay