Mechanism of action: SERM
__Figure 1. Schematic showing interaction of isoflavones and
__the human oestrogen receptor (adated from reference 60)
The estrogenic activity of isoflavones is relatively weak, of the order of 1000 times less than that of 17ß-estradiol. However, when consumed in relatively large amounts, plasma levels of isoflavone active metabolites are significant 23,24. Before menopause when endogenous estrogen levels are high, isoflavones may exert anti-estrogenic activity by competitive inhibition, preventing estrogen from binding to the estrogen receptor. During and after menopause when endogenous estrogens decline isoflavones produce a surrogate estrogen effect.
Isoflavones and their metabolites can preferentially activate the form of the estrogen receptor which predominates in brain, bone and heart (ER-ß) but show little activity against the form of estrogen receptor present in breast and uterine tissues (ER-α) 25 (Table 2). Isoflavones do not bind or activate the androgen receptor. 26
__Figure 2. ER-α and ER-ß receptors predominate in various tissues
| Compound |
Relative Binding Affinity |
| |
ER-α |
ER-ß |
| 17ß-estradiol |
100 |
100 |
| 2-OH-estrone |
2 |
0.2 |
| 5-androstenediol |
1 |
7 |
| 4-OH-tamoxifen |
257 |
232 |
| Raloxifene |
69 |
16 |
Isoflavones
Genistein
Daidzein |
4
0.1 |
87
0.5 |
|
Table 2. Relative binding affinity of compounds to ER-α and ER-ß
References
| Collins BM, McLachlan JA, and Arnold SF.23 |
Steroids 1997; 62 (4): 365-72. |
The estrogenic and antiestrogenic activities of phytochemicals with the human estrogen receptor expressed in yeast. |
| Miksicek RJ. 24 |
Proc Soc Exp Biol Med 1995; 208: 44-50. |
Estrogenic flavonoids: Structural requirements for biological activity. |
| Couse JF, Lindzey J, Grandien K, Gustafsson JA, and Korach KS. 25 |
Endocrinol 1997; 138 (11): 4613-21. |
Tissue distribution and quantitative analysis of estrogen receptor-alpha and estrogen receptor-beta messenger ribonucleic acid in the wild-type and ER-alpha knockout mouse. |
| Cato AC, Miksicek R, Schütz G, Arnemann J, and Beato M. 26 |
Embo J 1986; 5 (9): 2237-40. |
The hormone regulatory element of mouse mammary tumour virus mediates progesterone induction. |
| Adlercreutz H. 60 |
Bailliere’s Clin. Endocrinol. Metab. 1998; 12:605-625. |
Epidemiology of Phytoestrogens |
|
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