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Ginsenoside-Rb1 from Panax ginseng C.A. Meyer Activates Estrogen Receptor- and -ß, Independent of Ligand Binding

College of Life Science (JY.C., W.P., YJ.L.), Institute of Biotechnology, Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Korea; College of Pharmacy (SK.L.), Seoul National University, Seoul 151-742, Korea; and Department of Obstetrics and Gynecology (W.A.), Catholic Research Institutes of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea

Address all correspondence and requests for reprints to: YoungJoo Lee, Ph.D., Department of Bioscience and Biotechnology, Sejong University, Kwang-Jin-Gu, Seoul 143-747, Korea. E-mail: yjlee{at}sejong.ac.kr.

We studied the estrogenic activity of a component of Panax ginseng, ginsenoside-Rb1. The activity of ginsenoside-Rb1 was characterized in a transient transfection system, using estrogen receptor isoforms and estrogen-responsive luciferase plasmids, in COS monkey kidney cells. Ginsenoside-Rb1 activated both and ß estrogen receptors in a dose-dependent manner with maximal activity observed at 100 µM, the highest concentration examined. Activation was inhibited by the estrogen receptor antagonist ICI 182,780, indicating that the effects were mediated through the estrogen receptor. Treatment with 17ß-estradiol or ginsenoside-Rb1 increased expression of the progesterone receptor, pS2, and estrogen receptor in MCF-7 cells and of AP-1-driven luciferase genes in COS cells. Although these data suggest that it is functionally very similar to 17ß-estradiol, ginsenoside-Rb1 failed to displace specific binding of [³H]17ß-estradiol from estrogen receptors in MCF-7 whole-cell ligand binding assays. Our results indicate that the estrogen-like activity of ginsenoside-Rb1 is independent of direct estrogen receptor association.

This work was supported in part by grants from the Korean Science and Engineering Foundation (2000-20700-005-3; SK.L.), Korea Tobacco and Ginseng Corp. R&D Program 2000 (YJ.L.), Korean Ministry of Health and Welfare (HMP-00-O-21600-0009 to YJ.L.), and BK21 program (YJ.L.).

JY.C. and W.P. contributed equally to this work.

Abbreviations: CD-FBS, Charcoal-dextran stripped fetal bovine serum; E2, 17ß-estradiol; ER, estrogen receptor; ERE, estrogen-responsive element; PR, progesterone receptor.

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