Researches of Phytoestrogens

PHYTO-OESTROGEN TISSUE LEVELS IN BENIGN PROSTATIC HYPERPLASIA AND PROSTATE CANCER AND THEIR ASSOCIATION TO PROSTATIC DISEASES

Introduction and Objectives :: Aim of this study was to compare phytooestrogen tissue levels in men with small volume benign prostatic hyperplasia (BPH), enlarged BPH (i.e. benign prostatic enlargement, BPE) and prostate cancer (PC).Materal & Methods : Prostatic tissue samples of men on a western diet undergoing surgery for BPH (n=63) and PC (n=3 1) were collected and frozen at - 40 C”. Prior surgery, prostate volume was determined by transrectal ultrasound. In these tissue samples, Enterolactone- and Genistein-levels were determined in duplicates by monoclonal antibody-based immunoassays. We subsequently compared tissue levels in BPH- and PC-patients and studied the impact of prostate volume on Enterolactone and Genistein-tissue levels.Results : Enterolactone tissue levels were comparable in BPH and PC-patients and revealed no correlation to prostate volume. Genistein tissue levels tended to be lower in PC-patients (median: 8.0ngldry weight g) as compared to the entire BPH-group (ll.Ong/ dry weight g; p=O.O7). In addition, Genistein tissue levels were significantly higher in men with small BPH (median 20.9ngldly weight g) as compared to those with enlarged BPH (8.8ng/dry weight g; p=O.O23).Conclusion : Our data suggest an involvement of Genistein in the pathogenesis of BPH and, possibly, of PC; the role of Enterolactone seems to be less important.

Case-control study of phyto-oestrogens and breast cancer

Background: Phyto-oestrogens are a group of naturally occurring chemicals derived from plants; they have a
structure similar to oestrogen, and form part of our diet. They also have potentially anticarcinogenic biological activity. We did a case-control study to assess the association between phyto-oestrogen intake (as measured by urinary excretion) and the risk of breast cancer.

Methods: Women with newly diagnosed early breast cancer were interviewed by means of questionnaires, and a 72 h urine collection and blood sample were taken before any treatment started. Controls were randomly selected from the electoral roll after matching for age and area of residence. 144 pairs were included for analysis. The urine samples were assayed for the isoflavonic phyto-oestrogens daidzein, genistein, and equol, and the lignans enterodiol, enterolactone, and matairesinol. Findings After adjustment for age at menarche, parity, alcohol intake, and total fat intake, high excretion of both equol and enterolactone was associated with a substantial reduction in breast-cancer risk, with significant trends through the quartiles: equol odds ratios were 1·00, 0·45 (95% CI 0·20, 1·02), 0·52 (0·23, 1·17), and 0·27 (0·10, 0·69)—trend p=0·009—and enterolactone odds ratios were 1·00, 0·91 (0·41, 1·98), 0·65 (0·29, 1·44), 0·36 (0·15, 0·86)—trend p=0·013. For most other phytoestrogens there was a reduction in risk, but it did not reach significance. Difficulties with the genistein assay precluded analysis of that substance. Interpretation There is a substantial reduction in breastcancer risk among women with a high intake (as measured by excretion) of phyto-oestrogens—particularly the isoflavonic phyto-oestrogen equol and the lignan enterolactone. These findings could be important in the prevention of breast cancer.

Differential Effects of Dietary Phyto-oestrogens Daidzein and Equol on Human Breast Cancer MCF-7 Cells

Objective: The in vitro effects of two closely related phyto-oestrogens daidzein and equol on the oestrogen receptor positive human breast cancer cells MCF-7 were examined. There is differential metabolism of daidzein in humans, and the conversion of daidzein to equol by intestinal microbes occurs only in 30% of the population. The differential potency of these two compounds is thus of considerable importance since it may be likely that the relative risk of hormone-depaendent cancers may be higher in 'non-responders'. In the present study, we compared the ability of both these compounds to induce mRNA expression of the oestrogen-responsive pS2 gene, to compete with oestradiol for binding to the oestrogen receptor (ER) and to affect cellular proliferation. Our studies demonstrate that equol is a 100-fold more potent than daidzein in stimulating an oestrogenic response. Equol was also more effective than daidzein in competing with H-oestradiol for binding to the ER. Thesee results suggest that equol has a higher affinity for the ER. Both compounds stimulated the growth of MCF-7 cells in a concentration-dependent manner 10(-8)-10(-5)M. Although equol exhibits oestrogenic activity, exposure of MCF-7 cells to equol simultaneously with oestradiol was effective in reducing pS2 mRNA expression. This was not observed with daidzein. However, long-term exposure of MCF-7 cells to both daidzein and equol resulted in the downregulation of ER mRNA expression.

Effects of dietary phytoestrogens on core body temperature during the estrous cycle and pregnancy

Phytoestrogens, plant-derived nonsteroidal estrogens found in high abundance in most soy food products, have been studied for their potential beneficial effects against hormone-dependent cancers and age-related diseases. However, little is known about the influence of phytoestrogens on the brain or behavior. This brief review describes mainly our own studies in rodents that have examined the influence of dietary soy isoflavones on certain aspects of brain structure, learning, memory and anxiety along with the brain androgen-metabolizing enzyme, aromatase. These studies used a commercially available diet rich in phytoestrogens (Phyto-rich) vs. a custom diet relatively free of phytoestrogens (Phyto-free). The phytoestrogen content of each diet was determined by high-performance liquid chromatography analysis, circulating plasma phytoestrogen levels were quantified by gas chromatography mass spectroscopy and oncentrations of phytoestrogens in specific brain regions were measured by time-resolved fluoroimmunoassay (TR-FIA). Our studies showed that brain aromatase levels were not significantly altered by phytoestrogen diet treatments in perinatal, maternal or adult rats. However, volumes of the sexually dimorphic nucleus of the preoptic area (SDN-POA) were significantly affected by the Phyto-free diet treatment in male rats during adulthood, where SDN-POA volumes were smaller compared to Phyto-rich male values. Additionally, the Phyto-rich diet fed to adult male and female rats produced anxiolytic effects as assessed in the elevated plus maze vs. Phyto-free fed animals. Finally, when learning and memory parameters were examined in a radial arm maze testing visual–spatial memory (VSM), the diet treatments significantly changed the typical sexually dimorphic pattern of VSM. Specifically, adult Phyto-rich fed females outperformed Phyto-free fed females, while in males on the same diets, the opposite pattern of maze performance was observed. When female vs. male performance was compared, Phyto-rich females executed the VSM task in a manner similar to that of Phyto-free fed males, while Phytofree fed female’s VSM was comparable to Phyto-rich males. These results indicate that consumption of dietary phytoestrogens resulting in very high plasma isoflavone levels (in many cases over a relatively short interval of consumption in adulthood) can significantly alter sexually dimorphic brain regions, anxiety, learning and memory. The findings of these studies identify the biological actions of phytoestrogens, specifically isoflavones and their metabolites, found in animal soy-containing diets on brain and behavior and implicate the importance of phytoestrogens given the recognized significance of estrogens in brain and neural disorders, such as Alzheimer’s disease, especially in women.