Effekte von Estradiol und Raloxifen sowie der pflanzlichen Substanzen Agnus castus, Belamcanda chinensis und Silybum marianum im Brustgewebe der ovarektomierten Ratte im Hinblick auf das Mammakarzinomrisiko
Effects of estradiol and raloxifene and phytoestrogenes Agnus castus, Belamcanda chinensis and Silybum marianum in ovariectomized rat breast tissue in relation to breast cancer risk
von Jasmin Ebrahimkhil
Datum der mündl. Prüfung:2013-03-04
Betreuer:Prof. Dr. Wolfgang Wuttke
Gutachter:Prof. Dr. Michael Müller
Gutachter:Prof. Dr. Patricia Virsik-Köpp
EnglischMenopausal symptoms can affect the general health of women strongly negative. Not only women in the natural or surgical menopause, but also women with an antihormontherapy with tamoxifen or aromatase-inhibitors + /. GNRH analogues or even chemotherapy are affected. HRT, which is uncontroversial the most effective treatment for menopausal symptoms is a risk factor for breast cancer development. Despite several methodological study shortcomings, the recently published studies of the "Women's Health Initiative" and the "One Million Women Study" caused a stricter indication for the hormone replacement therapy today than years ago. In course of time more herbal products, including the phytoestrogenes with questionable positive, possibly estrogenic effects on perimenopausal symptoms are seen as alternatives to HRT. These are already being prescribed by doctors or are considered as harmless by women in the self-therapy and are taken as a food supplement. The literature contains few or controverse data about the effectiveness, mechanism of action, including interactions and the risk profile of the phytoestrogens. The current data situation does not allow any conclusive statement. The aim of this study was to prove molecular-biological effects (= expression) of the plant extracts Agnus castus, Belamcanda chinensis and Silybum marianum, the SERM raloxifene and 17ba-estradiol compared to the control group on the RNA expression in breast tissue of the ovx rat, which is considered as the established model in the study of the post-menopause. We used estrogene as a positive and raloxifene a negative controle. To analyze the questionable oestrogenic actions, effects of the plant extracts on estrogene-receptors (a/b) on m-RNA level was determind by gene expression studies (PCR). To answer the question of possible proliferative effects on mammary structures, we quantified the gene expression of PR-, IGF-1- and VEGF-mRNA using the PCR method. The determination of Aromatse mRNA gene expression by PCR was used to answer the question whether the tested plant extracts could potentially have an influence on the biosynthesis of estrogens. In addition to gene expression the comparison between the applicationforms p. g. and s. c. was also examinated.