Abstract # 2235 Event # 82:

Scheduled for Friday, June 22, 2007 09:30 AM-09:45 AM: Session 8 (North Main Hall C/D) Symposium

Estrogen/Isoflavone Interactions in Cynomolgus Macaques (Macaca fascicularis)

J. M. Cline and C. E. Wood
Wake Forest University School of Medicine, Section on Comparative Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1040, USA
     Dietary soy isoflavone "phytoestrogens" appear to decrease breast and endometrial cancer risk in human observational studies, but paradoxically stimulate breast cancer cells in culture, and cause uterine enlargement in rodents. Primate studies show clear species differences in response to isoflavones, and modulation of endogenous estrogen metabolism. Isoflavones are not estrogenic alone at up to 10 times dietary levels in cynomolgus monkeys (Wood et al., 2006); rather they reduce estrogen-induced proliferative responses of the breast and endometrium at dietary levels (Wood et al., 2006a). This effect may be mediated through lowering of bioavailable estrogens. Furthermore, individual isoflavone metabolites may have unique selective estrogen receptor modulator-like activity, acting as tissue-specific antagonists without agonist activity. Inter-individual variation in isoflavone absorption and metabolism contributes strongly to the degree of estrogen antagonistic effect in macaques. Rodent studies and human epidemiologic data suggest that timing of exposure and dose relative to endogenous estrogen concentrations are important determinants of effect, and studies of dietary soy on breast development and pubertal maturation are under way. Because soy isoflavones are both abundant in "monkey chow" and widely available as dietary supplements for human beings, these findings have broad relevance to the health of human and nonhuman primates.