Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Bovee, T.F. et al.

Bovee, Helsdingen, Rietjens, Keijer, Hoogenboom,

Rapid yeast estrogen bioassays stably expressing human estrogen receptors alpha and beta, and green fluorescent protein: a comparison of different compounds with both receptor types.

Previously, we described the construction of a rapid yeast bioassay stably expressing human estrogen receptor (hERalpha) and yeast enhanced green fluorescent protein (yEGFP) in response to estrogens. In the present study, the properties of this assay were further studied by testing a series of estrogenic compounds. Furthermore, a similar assay was developed based on the stable expression of human estrogen receptor beta (hERbeta). When exposed to 17beta-estradiol, the maximum transcriptional activity of the ERbeta cytosensor was only about 40% of the activity observed with ERalpha, but the concentration where half-maximal activation is reached (EC50), was about five times lower. The relative estrogenic potencies (REP), defined as the ratio between the EC50 of 17beta-estradiol and the EC50 of the compound, of the synthetic hormones dienestrol, hexestrol and especially mestranol were higher with ER, while DES was slightly more potent with ERbeta. The gestagens progesterone and medroxyprogesterone-acetate showed no response, whereas the androgen testosterone showed a very weak response. The anabolic agent, 19-nortestosterone showed a clear dose-related response with estrogen receptor but not beta. The phytoestrogens coumestrol, genistein, genistin, daidzein, daidzin and naringenin were relatively more potent with ERbeta. Ranking of the estrogenic potency with ER was: 17beta-estradiol >> 8-prenylnaringenin > coumestrol > zearalenone >> genistein >> genistin > naringenin. The ranking with the ERbeta was: 17beta-estradiol >> coumestrol > genistein > zearalenone > 8-prenylnaringen >> daidzein > naringenin > genistin >> daidzin. The hop estrogen 8-prenylnaringenin is relatively more potent with ERalpha. These data show that the newly developed bioassays are valuable tools for the rapid and high-throughput screening for estrogenic activity.[1]

References

Rapid yeast estrogen bioassays stably expressing human estrogen receptors alpha and beta, and green fluorescent protein: a comparison of different compounds with both receptor types. Bovee, T.F., Helsdingen, R.J., Rietjens, I.M., Keijer, J., Hoogenboom, R.L. J. Steroid Biochem. Mol. Biol. (2004) [Pubmed]

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