title: Recombinant cell bioassays for the detection of (gluco)corticosteroids and endocrine-disrupting potencies of several environmental PCB contaminants.
abstract: Sensitive and robust bioassays for glucocorticoids are very useful for the pharmaceutical industry, environmental scientists and veterinary control. Here, a recombinant yeast cell was constructed that expresses the human glucocorticoid receptor alpha and a green fluorescent reporter protein in response to glucocorticoids. Both the receptor construct and the reporter construct were stably integrated into the yeast genome. The correct and specific functioning of this yeast glucocorticoid bioassay was studied by exposures to cortisol and other related compounds and critically compared to a GR-CALUX bioassay based on a human bone cell. Although less sensitive, the new yeast glucocorticoid bioassay showed sensitivity towards all (gluco)corticoids tested, with the following order in relative potencies: budesonide >> corticosterone > dexamethasone > cortisol = betamethasone > prednisolone > aldosterone. Hormone representatives for other hormone nuclear receptors, like 17β-estradiol for the oestrogen receptor, 5α-dihydrotestosterone for the androgen receptor and progesterone for the progesterone receptor, showed no clear agonistic responses, whilst some polychlorinated biphenyls were clearly able to interfere with the GR activity.
authors.affiliation: RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Akkermaalsbos 2, 6708 WB Wageningen, The Netherlands. toine.bovee@wur.nl
authors.forename: Toine F H
authors.initials: TF
authors.lastname: Bovee
authors.forename: Richard J R
authors.initials: RJ
authors.lastname: Helsdingen
authors.forename: Astrid R M
authors.initials: AR
authors.lastname: Hamers
authors.forename: Bram A
authors.initials: BA
authors.lastname: Brouwer
authors.forename: Michel W F
authors.initials: MW
authors.lastname: Nielen
mesh_terms: D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D004703:Endocrine System / Q000187:drug effects*; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D015003:Yeasts / Q000235:genetics
chemical_list: D004785:Environmental Pollutants; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; C411470:glucocorticoid receptor alpha; D011078:Polychlorinated Biphenyls