Abstract
When applied to the screening of calf urine samples for anabolic androgens, the developed AR-LUX assay was able to identify androgen-treated animals with similar results as obtained by standard GC-MS analysis. However, both techniques should be regarded as complementary rather than interchangeable screening tools. Liquid samples confiscated at cattle farms outside theNetherlandswere found to generate a very strong response in the AR-LUX assay despite the fact that GC-MS analysis did not detect the presence of any anabolic compounds. Possibly, the samples contained a mixture of conventional androgenic compounds, each at undetectably low amounts and/or (novel) unknown compounds not tested for by GC-MS. These results emphasize the additional value of the developed AR-LUX assay.
Also, the AR-LUX assay was used to determine the androgenic activity of a number of aquatic environmental samples. A number of these samples were found to contain androgenic activity at varying concentrations. Interestingly, in 2 samples containing androgens, enhancing interactive mixture effects were observed, which were probably due to interactions by estrogenic compounds and estrogen receptor activation.
Our research furthermore indicates that certain established progestagens are able to activate ARE-mediated luciferase expression via progesterone receptors; we hypothesise preferentially through the progesterone receptor-α isoform. This indicates that androgen reporter assays based on the activation of the androgen receptor alone rather than on activation of a response element might produce results quite different from those observed in assay systems featuring multiple steroid receptors. This further emphasizes the notion that the AR-LUX assay is not merely detecting activation of the androgen receptor by androgens, but also allows for the detection of other androgenic substances that regulate gene expression via alternative pathways leading to activation of an established androgen response element.
Original language | English |
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Qualification | Doctor of Philosophy |
Awarding Institution |
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Supervisors/Advisors |
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Award date | 16 Dec 2003 |
Place of Publication | [S.l.] |
Print ISBNs | 9789058089779 |
DOIs | |
Publication status | Published - 16 Dec 2003 |
Keywords
- androgens
- growth promoters
- cattle
- anabolic steroids
- endocrine disruptors