2004 Annual Report 4.What were the most significant accomplishments this past year? D. Progress Report: This report serves to document research conducted under a Grant Agreement between ARS and the Center for Bioenvironmental Research, Tulane University. Additional details of research can be found in the report for the parent CRIS 6435-42000-017-00D, "Identify Mechanisms of Isoflavonoid Induction in Legumes and Their Phytoestrogenic Effects." Hormonal changes in post-menopausal women can increase the risk of developing breast cancer, bone loss, and reduced cardiovascular health. Populations consuming a diet high in soybean phytoestrogens (compounds that mimic estrogen) have lower incidences of several diseases, including breast and prostate cancer. Recently, research has shown that isoflavones, a group of phytoestrogens found in soybean derived foods, are compounds that reduce the risk of certain potential health problems when consumed in the diet. Identifying the phytoestrogenic activity of soybean isoflavones would benefit the nutritional health of the population in general, particularly women. Techniques are being determined by ARS scientists to manipulate phytoestrogen levels in soybean seed and soy-based products to maximize health benefits by their consumption. The effects of elicitors on the synthesis of isoflavonoids have been characterized by ARS scientists, however further studies were conducted this past year by collaborators from Xavier University using a soybean cell line developed at the Southern Regional Research Center (SRRC). Preliminary results from this work indicate novel isoflavonoids exist in cell lines which may have estrogenic activity. Collaborating scientists from Tulane University have performed a series of in vitro (laboratory) bioassays using various phytoestrogen compounds extracted from soybean seeds treated with elicitors that induce phytoestrogens. Inducible compounds in soybean seed known as glyceollins were purified and used in several animal cell assays, demonstrating that these compounds block the growth of hormone-dependent breast cancer cells and indicating their potentially useful phytoestrogenic activity. In vivo (animal) studies using the glyceollins have begun to determine their potential therapeutic value. An in vivo study being conducted at Tulane University School of Medicine is ongoing using a nude mice model with subcutaneous injections of the glyceollins. The ability of the glyceollins to inhibit MCF-7 breast cancer growth will be determined. Also, 35 kg of glyceollin-enriched soy protein isolate was produced with the assistance of Solae Corporation. Two separate feeding studies examining the effects of the glyceollin-enriched soy protein isolate on breast cancer inhibition are underway at both Wake Forest University and Tulane University School of Medicine. Also, several herbal supplements containing phytoestrogens were examined for estrogenic, androgenic (hormone that causes the development and maintenance of masculine characteristics), and glucocorticoid (hormone involved in carbohydrate, protein, and fat metabolism) activity at Xavier University using several in vitro assays. Several of the supplements containing soybean isoflavonoids exhibited significant estrogenic activity. No supplement was found to induce androgen or glucocorticoid activity. Thus, some dietary supplements recommended for treatment of menopausal symptoms can stimulate estrogenic responses, but others do not despite claims to the contrary. IMPACT: This research could lead to a better understanding of the effects of induced soybean-derived isoflavonoids (plant compounds) on human health and may lead to alternative or value-added uses of soybean (legume) isoflavonoids. Also, research on the estrogenic activity of herbal supplements will impact human health, particularly women's health, and lead to better regulation guidelines and consumer choices.