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Selective Effects of Genistein, a Soybean Isoflavone, on B-Lymphopoiesis and Bone Loss Caused by Estrogen Deficiency¹

Department of Food Science (Y.I., M.O., X.W., S.I.), The National Institute of Health and Nutrition, Tokyo 162, Japan; Department of Biochemistry (C.M., Y.O., T.Su.), School of Dentistry, Showa University, Tokyo 142, Japan; Exploratory Research Laboratories III (T.Sa., Y.U.), Daiichi Pharmaceutical Company Ltd., Tokyo 134, Japan; Department of Radiology (M.I.), School of Medicine, Nagasaki University, Nagasaki 852, Japan; and Department of Biochemistry (C.M.), School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji 192, Japan

Address all correspondence and requests for reprints to: Yoshiko Ishimi, Department of Food Science, The National Institute of Health and Nutrition. 1–23-1 Toyama, Shinjuku-ku, Tokyo 162, Japan. E-mail ishimi{at}nih.go.jp

Genistein, an isoflavone abundantly present in soybeans, has structural similarity to estrogen, suggesting that genistein may act as a phytoestrogen. To examine the possible role of genistein in hemopoiesis and bone metabolism, female mice were either sham-operated or ovariectomized (OVX), and selected OVX mice were administered genistein for 2–4 weeks (0.1–0.7 mg/day) or 17ß-estradiol (E₂; 0.01–0.1 µg/day) sc, using a miniosmotic pump (Alza Corp., Palo Alto, CA). In OVX mice, uterine weight declined but was completely restored by E₂ administration. In contrast, genistein did not demonstrate a reversal of the OVX-induced uterine atrophy. The number of bone marrow cells markedly increased, 2–4 weeks after OVX, and most of these were B220-weakly positive pre-B cells. The increased B-lymphopoiesis was completely restored, not only by E₂ but also by genistein administration. In OVX mice, the trabecular bone volume of the femoral distal metaphysis, measured by microcomputed tomography scanning and dual-energy x-ray absorptiometry, was markedly reduced; and genistein restored this, as did E₂. These results indicate that genistein exhibits estrogenic action in bone and bone marrow, to regulate B-lymphopoiesis and prevent bone loss, without exhibiting estrogenic action in the uterus. Phytoestrogens may be useful for preventing bone loss caused by estrogen deficiency in females.

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