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Estrogenicity of Isoflavones on Human Endometrial Stromal and Glandular Cells

Section of Reproductive Endocrinology (U.A.K., C.A.H.A., M.B., A.A.), Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520; and Department of Histology and Embryology (U.A.K.), Akdeniz University School of Medicine, Antalya, Turkey 07070

Address all correspondence and requests for reprints to: Aydin Arici, M.D., Section of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520-8063. E-mail: aydin.arici{at}yale.edu.

Abstract

Endometrium consists of different cell populations such as epithelial and stromal cells and is mainly regulated by sex steroids. Isoflavones are plant-derived estrogenic compounds that have estrogenic and antiestrogenic properties in a cell-specific manner. We hypothesized that one of the potential health benefits of isoflavones may be their ability to regulate endometrial cell function. The present study was conducted to assess estrogenic and/or antiestrogenic effects of isoflavones (genistein, genistin, daidzein, and daidzin) in cultured human endometrial stromal and glandular (Ishikawa) cells by MTT colorimetric cell proliferation assay, proliferating cell nuclear antigen expression, and alkaline phosphatase activity assays. Experiments were performed in a time- (24–96 h) and concentration-dependent (10^-12 to 10^-5 M) manner. All isoflavones used in the present study induced endometrial stromal and Ishikawa cell proliferation when compared with control (vehicle) group in a time- (at 48 h and afterward) and concentration-dependent manner (at 10^-8 M and above) (P < 0.05). However, isoflavones (at 10^-8 and above concentrations) were also antiestrogenic when combined with estradiol (E₂) (P < 0.05). The isoflavones revealed a weak estrogenic activity (39–67% less than E₂) as assessed by alkaline phosphatase activity (P < 0.05), but when administered together with E₂, they antagonized estrogen induced alkaline phosphatase activity by 36–89% (P < 0.05). We conclude that, although isoflavones alone have weak estrogenic effects on endometrial stromal and glandular cells, in the presence of E₂ they act as antiestrogens.

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