Der Einfluss von Sojaisoflavonen auf hormonabhängige Organe - tierexperimentelle Studien im Modell der weiblichen Wistar Ratte

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  • Tina Blei

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Abstract
The incidence of breast cancer in Asian countries is approximately three times lower than in western countries. Epidemiological studies showed that the lifestyle and the nutritional habits seem to play an important role in cancer etiology. The traditional Asian diet is rich in soy, which is the main source of the isoflavones (IF) genistein, daidzein and glycitein. Isoflavones are plant-derived compounds with structural similarity to 17β-estradiol and can exert estrogenic effects via binding to estrogen receptor. The aim of this study was to investigate the potential beneficial or adverse health aspects of isoflavones in the female organism, especially in the breast with respect to the impact on the risk of developing breast cancer.
In this work, we investigated the impact of the dose, the time point of exposure and the influence of dietary fat on the action of isoflavones. Three independent animal experiments in the female Wistar rat were conducted. For analysis of a dose response relationship animals received lifelong an isoflavone-depleted diet (IDD) or an isoflavone enriched diet with two different concentrations (IRD50 with 69ppm and IRD400 with 506ppm IF aglycone equivalents) for simulating the traditional Asian dietary habits. Body weight development, puberty onset, and the estrus cycle length were determined of growing rats. At the age of 80 days (PND80) proliferative (PCNA) and estrogenic (PR) activity were immunohistochemically analyzed in the mammary gland of intact rats. Body weight, viszeral fat mass, adipocyte size, uterine wet weight, uterine and vaginal epithelial height were examined. In order to analyze estrogen sensitivity of the mammary gland IDD, IRD50 and IRD400 rats were ovariectomized at PND80 and treated either with vehicle (OVX) or 17β- estradiol (E2, 4 μg/kg bw/d). To investigate the short-term effect of isoflavone exposure a second experiment was performed. Adult rats were exposed to IDD or IRD400 from PND 80 for 17 days and an uterotrophic assay was performed as described above. Like in the first experiment the responsiveness of the mammary gland was analyzed. In the last experiment we investigated the influence of dietary fat in combination with a lifelong isoflavone exposure. Therefore in the third experiment we supplemented the IDD and IRD400 with an additional fat source consisting of sunflower oil (40 kJ% energy of fat; IDD HF, IRD HF). In addition animals were subjected to lifelong exposure with one of the low fat diets (9 kJ% energy of fat; IDD LF, IRD LF) and one group per diet was switched to the HF diet at PND 21. The same groups, treatments and parameters were analyzed as mentioned in experiment one.
Lifelong exposure (experiment 1) to IRD400 resulted in decreased proliferative and estrogenic response of the mammary gland in E2 treated animals, which was not achieved
1
through IRD50. We observed a reduced estrogen sensitivity of this organ through a long-term high isoflavone intake (IRD400). Short-term exposure (experiment 2) of isoflavones resulted in the opposite effect. IRD400 caused an induction of proliferation and a higher estrogenic activity compared to IDD. This result brought about serious concerns in terms of the safety of using soy supplements and, therefore further investigations have to be carried out. Another aspect was the observation of an advanced puberty onset and shortened estrus cycle length in the lifelong IRD exposed animals which led to unwanted side-effects due to inceased lifetime estrogen exposure. In addition the main results of the first two animal experiments showed a strong influence of the given dose and the importancy of the duration of exposition on isoflavone action and should be taken into consideration. Dietary fat did not influence the proliferative response of isoflavone exposed animals. Furthermore, we observed an induction of serum HDL through IRD in intact animals. This indicates potential mechanisms by which soy isoflavones exert beneficial effects on the fat metabolism. This can probably be used to develop new therapeutic strategies in the prevention of obesity and cardiovascular diseases like arteriosclerosis.
Original languageGerman
Place of PublicationKöln
PublisherDeutsche Sporthochschule Köln
Number of pages145
Publication statusPublished - 2014

ID: 1747000

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