Recombinant cell bioassays for the detection of (gluco)corticosteroids and endocrine-disrupting potencies of several environmental PCB contaminants |
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Authors: | Toine F H Bovee Richard J R Helsdingen Astrid R M Hamers Bram A Brouwer Michel W F Nielen |
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Institution: | (1) RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Akkermaalsbos 2, 6708 WB Wageningen, the Netherlands;(2) BioDetection Systems B.V. (BDS), Kruislaan 406, 1098 SM Amsterdam, the Netherlands;(3) Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB Wageningen, the Netherlands |
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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. |
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