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Investigating Mechanisms of Action of Environmental Estrogens Using Yeast Genetic Systems

Undergraduate #9
Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology

Corey Key - Alabama A&M University


Environmental Estrogens are synthetic compounds that mimic estrogen’s biological effects. Previous studies have demonstrated one such compound, Bisphenol A(BPA)’s ability to initiate estrogen receptor(ER) – dependent transcription. Concerns of BPA’s estrogenic properties prompted consumer product manufacturers seeking alternatives for the chemical following consumer lobbying. A successful push for safer alternatives has brought about “BPA Free” labeling and the implementation of BPS and other bisphenol compounds as viable substitutes, but suspicions of similarities in harmful effects as endocrine disruptors have raised new concerns. Estrogen mimicking bisphenol compounds are thought to be capable of enhancing or inhibiting enzymatic activity and protein synthesis in binding human estrogen receptor(hER) thus activating or inhibiting transcription and hER mediated cellular responses. Homeostatic imbalance of the estrogen/estrogen receptor function results in the manifestation innumerable diseases, syndromes and medical conditions. In this study potential estrogenic activity of selected bisphenol compounds Bisphenol S(BPS), Bisphenol F(BPF), and Bisphenol AF(BPAF) were compared to BPA and estrogen using two yeast genetic assays: Yeast-two hybrid bioassay and a Transactivation assay. Quantitative analysis of bisphenol compounds’ ability to induce a biologically active dimer with (hER) was monitored via activation of lacZ reporter gene within an expression vector of the PCY2 yeast strain. The construct of the PCY2 yeast strain expresses hER and reports activity through the activation of a Gal-1 promoter and a downstream lacZ reporter gene. Preliminary results have indicated BPAF at micro-molar concentrations to be alarmingly more competent(potent) in its ability to induce human estrogen receptor dimerization than that of BPA while BPS and BPF appear to not have the potential to induce the formation of an active dimer. Results have also shown BPAF to be potentially toxic at the concentration of 1 molar. The effects of bisphenols compounds monitored in yeast systems present relative data to evaluate potential consequences of exposure to bisphenol compounds “In Vivo”.

Funder Acknowledgement(s): NSF ASSURE

Faculty Advisor: Cameron Q. Sheeler, cameron.sheeler@aamu.edu

Role: I was responsible for the project from start to completion with the guidance of my mentor, literature review, concentration calculations, dose response curves, running multi-day experiments and interpreting results.

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This material is based upon work supported by the National Science Foundation (NSF) under Grant No. DUE-1930047. Any opinions, findings, interpretations, conclusions or recommendations expressed in this material are those of its authors and do not represent the views of the AAAS Board of Directors, the Council of AAAS, AAAS’ membership or the National Science Foundation.

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