Title

Ability of Structurally Diverse Natural Products and Sythetic Chemicals to Induce Gene Expression Mediated by Estrogen Receptors from Various Species

Abstract

The ability of 14 structurally diverse estrogenic compounds to induce reporter gene expression mediated by estrogen receptors (ERs) from different species was examined. MCF-7 cells were transiently transfected with a Gal4-regulated luciferase reporter gene (17m5-G-Luc) and Gal4-ER chimeric receptors containing the D, E and F domains of the human α (Gal4-hERαdef), mouse α (Gal4-mERαdef), mouse β (Gal4-mERβdef), chicken (Gal4-cERαdef), green anole (Gal4-aERαdef), Xenopus (Gal4-xERdef) or rainbow trout α ERs (Gal4-rtERαdef). The efficacy of 17β-estradiol (E2) in inducing reporter gene expression was similar among the different constructs overall, with EC50 values ranging from 0.05 to 0.7 nM. However, Gal4-rtERαdef had an EC50 value at 37 °C of 28 nM, though at 20 °C an EC50 value of 1 nM was observed. Despite a similar response to E2 treatment among the ERs, many differences were observed in the magnitude of the response to other structurally diverse chemicals. For example, coumestrol induced Gal4-mERβdef- and Gal4-aERdef-mediated reporter gene expression 164- and 8-fold greater, respectively, than mediated with the other Gal4-ERs. As well, in contrast to results with other Gal4-ERs, α-zearalenol consistently induced Gal4-rtERαdef-mediated reporter gene activity at lower concentrations than did E2. Overall, the results demonstrate that selected estrogenic compounds exhibit a differential ability to induce reporter gene activity mediated by ERs from different vertebrate species. These data also highlight the importance of incubation temperature when examining rtERα-mediated activity.

Department(s)

Biological Sciences

Sponsor(s)

United States. Environmental Protection Agency

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2002 Elsevier, All rights reserved.


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