期刊
ENDOCRINOLOGY
卷 150, 期 5, 页码 2446-2453出版社
ENDOCRINE SOC
DOI: 10.1210/en.2008-1235
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资金
- National Institutes of Health (NIH) [DK 059389, T32-HL-07973-05]
- Susan G. Komen Breast Cancer Foundation [BCTR0601198]
- Office of Naval Research [N0001406-1-1136]
- United States Department of Agriculture [59-6435-7-188]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007973] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK059389] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [F31GM069318] Funding Source: NIH RePORTER
The primary induced isoflavones in soybean, the glyceollins, have been shown to be potent estrogen antagonists in vitro and in vivo. The discovery of the glyceollins' ability to inhibit cancer cell proliferation has led to the analysis of estrogenic activities of other induced isoflavones. In this study, we investigated a novel isoflavone, glycinol, a precursor to glyceollin that is produced in elicited soy. Sensitive and specific in vitro bioassays were used to determine that glycinol exhibits potent estrogenic activity. Estrogen-based reporter assays were performed, and glycinol displayed a marked estrogenic effect on estrogen receptor (ER) signaling between 1 and 10 mu M, which correlated with comparable colony formation of MCF-7 cells at 10 mu M. Glycinol also induced the expression of estrogen-responsive genes (progesterone receptor and stromal-cell-derived factor-1). Competitive binding assays revealed a high affinity of glycinol for both ER alpha (IC50 = 13.8 nM) and ER beta (IC50 = 9.1 nM). In addition, ligand receptor modeling (docking) studies were performed and glycinol was shown to bind similarly to both ER alpha and ER beta. Taken together, these results suggest for the first time that glycinol is estrogenic and may represent an important component of the health effects of soy-based foods. (Endocrinology 150: 2446-2453, 2009)
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