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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/24960

Title: Dual effects of phytoestrogens result in u-shaped dose-response curves
Authors: Almstrup, Kristian
Fernández, Mariana F.
Petersen, Jørgen
Olea, Nicolás
Skakkebæk, Niels
Leffers, Henrik
Issue Date: 2002
Abstract: Endocrine disruptors can affect the endocrine system without directly interacting with receptors, for example, by interfering with the synthesis or metabolism of steroid hormones. The aromatase that converts testosterone to 17β-estradiol is a possible target. In this paper we describe an assay that simultaneously detects aromatase inhibition and estrogenicity. The principle is similar to that of other MCF-7 estrogenicity assays, but with a fixed amount of testosterone added. The endogenous aromatase activity in MCF-7 cells converts some of the testosterone to 17β-estradiol, which is assayed by quantifying differences in the expression level of the estrogen-induced pS2 mRNA. Potential aromatase inhibitors can be identified by a dose-dependent reduction in the pS2 mRNA expression level after exposure to testosterone and the test compound. Using this assay, we have investigated several compounds, including synthetic chemicals and phytoestrogens, for aromatase inhibition. The phytoestrogens, except genistein, were aromatase inhibitors at low concentrations (< 1 μM) but estrogenic at higher concentrations (≥ 1 μM), resulting in U-shaped dose–response curves. None of the tested synthetic chemicals were aromatase inhibitors. The lowdose aromatase inhibition distinguished phytoestrogens from other estrogenic compounds and may partly explain reports about antiestrogenic properties of phytoestrogens. Aromatase inhibition may play an important role in the protective effects of phytoestrogens against breast cancer.
Publisher: National Institute of Environmental Health Sciences
Description: 'Reproduced with permission from Environmental Health Perspectives'
Keywords: Aromatase inhibitors
Endocrine disruptors
U-shaped dose-response curves
URI: http://hdl.handle.net/10481/24960
ISSN: 0091-6765
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: Almstrup, K.; et al. Dual effects of phytoestrogens result in u-shaped dose-response curves. Environmental Health Perspectives, 110(8): 743-748 (2002). [http://hdl.handle.net/10481/24960]
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