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Soy Isoflavones, Estrogens and Growth Factor Signaling By Stephen Barnes, Ph.D. and Helen Kim, Ph.D. Soybeans are unique among beans because they contain compounds called isoflavones. Because these molecules have structures very similar to the body's natural estrogens (hence the name plant- or phyto-estrogens), major research efforts are directed at understanding what isoflavones do in our bodies when we eat soy. Soy Isoflavones How do soy isoflavones fit in? Genistein, the most abundant isoflavone in soybeans, binds only weakly with ER alpha, but complexes with ER beta almost as well as estrogen does (5). This probaby explains genistein's ability to support bone health in ovariectomized rats (6). The predominance of ER beta in the cardiovascular system suggests that soy isoflavones may be partly responsible for the lower incidence of heart disease in soy-consuming countries (the FDA has approved an official claim that 25 grams of soy protein per day, as part of a healthy diet low in cholesterol and saturated fat, may reduce risk of heart disease). References (1) Beresford SA. Weiss NS. Voigt LF. McKnight B. Risk of endometrial cancer in relation to use of oestrogen combined with cyclic progestation therapy in postmenopausal women. Lancet 1997;349:458-61. (2) Beral V, Bull D, Doll R, Key T, Peto R, Reeves G, Calle EE, Heath CW, Coates RJ, Liff JM, Franceschi S, Talamini R, Chantarakul N, Koetsawang S, Rachawat D, Morabia A, Schuman L, Stewart W, Szklo M, Bain C, Schofield F, Siskind V, Band P, Coldman AJ, Gallagher RP, et al. Breast cancer and hormone replacement therapy - collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 1997;350:1047-1059. (3) Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA: Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 1996;93:5925-5930. (4) Onoe Y, Miyaura C, Ohta H, Nozawa S, Suda T. Expression of estrogen receptor beta in rat bone. Endocrinology, 1997;138:4509-4512. (5) Kuiper GGJM, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology, 1997;138:863-870. (6) Blair H, Jordan SE, Peterson TG, Barnes S. Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats. J Cell Biochem, 1996;61:629-637. (7) Greenwald P: Principles of Cancer Prevention. Diet and Nutrition. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds): "Cancer: Principles and Practice of Oncology", 3rd Edition, Philadelphia, JB Lippincott, 1989, pp 167-180. (8) Ingram D, Sanders K, Kolybaba M, Lopez D. Case-control study of phyto oestrogens and breast cancer. Lancet, 1997;350(9083):990-994. (9) Guttmacher AE, Marchuk DA, White RI, Jr. Hereditary hemorrhagic telangiectasia. New Engl J Med, 1995;333:918-24. (10) Korzenik JR, Barnes S, White RI, Jr. A pilot study of soy protein isolat in the treatment of hereditary hemorrhagic telangiectasia (HHT): possible efficacy in HHT associated epistaxis, gastrointestinal hemorrhage and migraine. Am J Clin Nutr, accepted for publication. (11) McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, Jackson CE, Helmbold EA, Markel DS, McKinnon WC, Murrell J, et al. Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary hemorrhagic telangiectasia type 1. Nature Genetics. 1994;8:345-51. (12) Kim H, Peterson TG, Barnes S. Mechanisms of action of the soy isoflavone genistein: emerging role of its effects through transforming growth factor beta signaling pathways. Am J Clin Nutr, accepted for publication. About the authors Stephen Barnes, Ph.D. is professor in the Department of Pharmacology & Toxicology, University of Alabama at Birmingham. He is also director of the UAB Comprehensive Cancer Center Mass Spectrometry Care Facility. He obtained his Ph.D. in biochemistry in 1970 from the Imperial College of Science and Technology, University of London. Helen Kim, Ph.D. is research associate professor in the Dept. of Pharmacology & Toxicology at the University of Alabama at Birmingham. Her Ph.D. in biophysics was obtained from the University of Virginia in 1983. Reprinted with permission from The Soy Connection newsletter, Volume 6, No. 2, Spring 1998. More information about the newsletter can be obtained by writing to: Editor, The Soy Connection P.O. Box 237 Jefferson City, MO 65102 Isoflavone articles from The Soy Connection newsletter for registered dietitians, selected physicians and family and consumer science professionals... Isoflavones: New Frontier In Nutrition Interest in Isoflavones Continues to Increase Soy Isoflavones, Estrogens and Growth Factor Signaling Absorption and Metabolism of Isoflavones Additional isoflavone information.. Isoflavone Concentration in Soyfoods . . .