Isoflavone estrogens

WS-7528 [132147-69-4][VI] a nonsteroidal estrogen, is an isoflavone which has been isolated from Streptomjces sp. No. 7528 and is an estrogen agonist. It inhibits [3ff]-estradiol binding to its receptor in rat uterine cytosol at an inhibitor for 50% of the rats tested (IC q) concentration of 5.7 nM. It also induces the growth of estrogen-dependent human breast cancer cell line MCE-7 (7). 

Many stilbenelike thiophene compounds have been prepared for a study of estrogenic activity, especially by Buu-Hoi et al. Thiophene derivatives of nonhydroxylated stilbene types showed no significant activitywhereas weak estrogenic activity was found in 5-acetyl-, 5-propionyl-, and 5-benzoyl-2-(-stilbenyl)thiophene. 1-Bromo-l,2-diphenyl-2-(5-bromo-2-thienyl)ethylene (258) was found to inhibit body growth and to produce extensive testicular atropy in male rats. A thiophene analog of estrogenic isoflavones (259)... 

The individual role of isoflavones contained in soy protein compared to isoflavones alone has not been systematically studied. In addition, it is possible that some of the minor components of soy also play a biological role. Nevertheless, in terms of bone health, the benefit of soy diets is largely attributed to the isoflavones due to their weak estrogenic activity and potential to alleviate the estrogen loss following the menopause. 

ISHIMI Y, MIYAURA 0, OHMURA M, ONOE Y, SATO T, UCHIYAMA Y, ITO M, WANG X, SUDA T and IKEGAMI s (1999) Selective effects of genistein, a soybean isoflavone, on B-lymphopoiesis and bone loss caused by estrogen deficiency. Endocrinol 140, 1893-1900. 

It has been shown that in postmenopausal women habitually high intakes of dietary isoflavones are associated with higher bone mineral density (BMD) values at both the spine and hip region (Mei et al, 2001). It is conceivable that an isoflavone-rich diet may help to reverse the state of secondary hyperparathyroidism associated with estrogen withdrawal and hence lower the rate of bone turnover in postmenopausal women, thus reducing the risk of osteoporosis (Valtuena et al, 2003). Phytoestrogens could be used as natural SERMs (Brzezinski and Debi, 1999) and some studies (Setchell, 2001 and refs therein) support such an idea since the molecular targets of... 

In some animals, consumption of a phytoestrogen-rich diet can cause temporary infertility and reproductive system disorders (Irvine, 1999). In humans, lower testosterone levels and a decline in human semen quality over the past century have been luiked to increased exposure to environmental endocrine disrupters (EDCs) (Sharpe and Skakkebaek, 1993). Furthermore, cases of sexual impotence have been reported in males exposed to synthetic estrogens in the pharmaceutical industry (Mattison et al., 1990). If this might be the case, the fetal-prepubertal period and Sertoli cell development would be of critical importance (Sharpe and Skakkebaek, 1993). However, an adverse effect of phytoestrogens on male fertility has yet to be proven. Recent work (Mitchell et al., 2001) addressing this point led to the conclusion that up to 40 mg/day of isoflavones over a two-month period had no effects on gonadotrophin and... 

DOERGE D R and SHEEHAN D M (2002) Goitrogenic and estrogenic activity of soy isoflavones. Environ Health Perspect. 110 (Suppl 3) 349-53. 

SETCHELL K D (2001) Soy isoflavones-benefits and risks from nature s selective estrogen receptor modulators (SERMs). J Am Coll Nutr. 20 (5 Suppl) 354S-362S. 

Isoflavones also have a diphenylpropane structure in which the B ring is located in the C3 position. They have structural analogies to estrogens, such as estradiol, with hydroxyl groups at the C7 and C4 positions (Shier and others 2001). 

The three main classes of phytoestrogens (and common food sources) are isoflavones (soybeans), lignans (cereals and oilseeds such as flaxseed), and coumestans (alfalfa sprouts). The biologic potency of phytoestrogens varies and is less than that of synthetic estrogen. 

Estrogenic Glycosides (Isoflavones, Coumestans) Coumarin Glycosides Goitrogenic Glycosides Other Glycosides... 

The phytoestrogens (isoflavones) contain a flavone nucleus. Examples of isoflavones are genistein, formononetin and coumestrol, all with potent estrogenic activity. Soybean isoflavones are a concern in human nutrition because of their estrogenic benefits. 

The Japanese diet differs in many aspects from its Western counterpart, not only in consumption of soy but also of fish. To date, however, soy alone appears to have attracted the attention of researchers. The structural similarity between the isoflavones contained in soy and estrogen has perhaps made it conceptually easier to associate soy consumption and the low incidence of hot flushes in Japanese women. This may prove to be too simplistic as it is highly likely that a combination of nutrients, rather than just one compound, may determine the favorable health effects of the diet. 

Phytoestrogens are a diverse group of polyphenolic non-steroidal plant compounds that bind to human estrogen receptors (Cos et al., 2003). The best studied of these compounds are the isoflavones, the phytoestrogens present in soy and red clover. 

The glycosides forms of the isoflavones have a weaker estrogenic action compared with their aglycone counterparts. In fact, they bind weakly to both ERot and ERP and the receptor-dependent transcriptional expression is poor. Once the glucose molecule is removed, the isoflavones bind more strongly to the estrogen receptor (Morito et al., 2001). 

Equol [7-hydroxy-3-(4 -hydroxyphenyl)-chroman] is a nonsteroidal estrogen of the isoflavone class. It is exclusively a product of intestinal bacterial... 

Isofavonoids have a substituent at C-3. Examples are genistein and for-mononetin (see Fig. 11.11, below). Isoflavones exert estrogenic activity in mammals, interfere with reproduction in birds, and may render farm animals infertile. For example, sheep feeding on isoflavonoid-containing Trifolium suh-terraneum suffer reduced lambing (Harborne, 1993). 

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