The Secret of Soy,What is Soy Isoflavones?Function of Natural Genistein?Soy Bean Extract.

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Estrogenic Effects of Genistein.

Soy Bean Extract INCI Name Glycine Soja Extract Soy Isoflavones Genistein Daidzein CAS 84776-91-0 Genistein CAS 446-72-0 Daidzein CAS486-66-8 photo picture image The phytoestrogen genistein is present naturally as several ?-glucosides, which are metabolized by intestinal microflora to genistein. Genistein, a planar molecule with an aromatic A ring, has a chemical structure similar to steroidal estrogens, and its ability to behave as an estrogen in various tissues has been widely described. Observations of phytoestrogens' estrogenic properties date back to the 1950s, when it was discovered that the diadezan metabolite equol was the compound responsible for reduced reproductive capacity in sheep grazing on clover. Subsequently, countless studies have been conducted to characterize the hormonal effects of phytoestrogens including genistein's estrogenic and presumed antiestrogenic properties.

 Genistein has significant estrogenic properties in both in vitro and in vivo models. Genistein binds to the estrogen receptor (ER), although its binding affinity is several-fold weaker than that of estradiol. Genistein can also activate a number of estrogen-responsive genes in vitro, including pS2 and c-fos. Furthermore, when administered at low doses, genistein stimulates the growth of ER-positive (ER+) breast cancer cells. Findings in other tissue systems support the estrogenicity of genistein. For example, genistein is uterotrophic in a variety of species, resulting in impaired reproductive activity and increases in uterine wet weights. It is important to note that some studies have failed to see any effect of genistein on the uterus, including alterations in wet weight. Furthermore, findings with coumestrol, a more estrogenic phytoestrogen than genistein, indicate that although coumestrol increases uterine wet weights, it does not increase uterine DNA content or alter other indicators of more true estrogenic activity. Thus, an increase in uterine wet weight alone does not necessarily indicate that genistein has estrogenic properties.

 In addition to directly binding to the ER, genistein may indirectly affect estrogenicity through inhibition of the cytochrome P450 enzyme CYP1A1. It has recently been shown that genistein is a noncompetitive inhibitor of the CYP1A1 enzyme, which apart from playing a role in the metabolism of carcinogens, is responsible for the metabolic degradation of 17Beta-estradiol. Thus, it is possible that genistein-mediated inhibition of estradiol degradation could result in higher levels of circulating estradiol and thus elevated ER activity.

 Genistein has estrogenic effects on the hypothalamic/pituitary axis in ovariectomized Sprague-Dawley rats. Human studies indicate that high soy intake can disrupt the hypothalamic/pituitary/gonadal axis in premenopausal women similar to that seen in animal models. This perturbation is not seen in postmenopausal women, suggesting a differential effect of soy/genistein on pre- and postmenopausal women. Finally, genistein may exert beneficial effects on bone, cardiovasculature, and lipid profiles, all of which are effects characteristic of estrogen. Taken together, these studies indicate that genistein can behave as an estrogen and can mediate mitogenic effects via the ER.

 Estrogens have long been identified as important mitogens in the breast and thus are associated with an increase in breast cancer risk. This is evidenced by the link between reproductive factors, including ages of first menarche, first pregnancy, and menopause, and breast cancer risk. This is further supported by studies showing that elevated concentrations of estrogens in serum and urine are associated with increased postmenopausal breast cancer risk. Additionally, estrogens induce mitogenic effects in both in vitro and in vivo models of breast cancer. The role of estrogen in this disease is supported by the fact that removal of ovarian estrogens by bilateral ovariectomy or use of tamoxifen (which blocks ER in the mammary gland) significantly reduces breast cancer risk. Because estrogen exposure presumably increases breast cancer risk, evidence showing that genistein acts in an estrogenic fashion is puzzling in light of the in vitro reports of genistein as an anticancer agent. To address studies that demonstrate the protective effects of genistein in in vitro and in vivo breast cancer models, it is important to determine whether genistein has antiestrogenic properties as well.

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citations1.The Secret of Soy,What is Soy Isoflavones?Function of Natural Genistein?Soy Bean Extract.

last edit date:6th,May.2009.