Role of Peroxisome Proliferator-Activated Receptor γ and Estrogen Receptors in Mediating the Anti-Mitogenic Actions of Phytoestrogens

Most Western countries face high and increasing rates of cardiovascular disease (CVD). Each year, heart disease kills more people than cancer. The increasing risk of CVD in woman after postmenopausal changes suggests that estrogen has cardioprotective effects. It is well known that estrogen binds to estrogen receptors (ER) and mediates its effects via different pathways and thereby influences various systems in the male and female physiology. Phytoestrogens, natural constituents of many plants, seeds and grains are oestrogen like ligands with numerous effects to the human body. They are similar to estrogens and bind to ERs, they are supposed to mimic the effects of estrogens and mediate these acitivities via ERs. However, recent findings suggest that phytoestrogens bind to PPARγ receptors. Together with the fact, that the protective effects of the phytoestrogen genistein are not blocked by ER antagonist and that PPARγ agonists are also cardioprotective we investigated, whether the protective action of phytoestrogens may be PPARγ mediated. Role of PPAR-Υ and ER in mediating the anti-mitogenic actions of phytoestrogens Universitätsspital Zürich Departement Frauenheilkunde Vorsitzender: Prof. Dr. med. R. Zimmermann Klinik für Reproduktionsendokrinologie Direktor: Prof. Dr. med. B. Imthurn Arbeit unter der Leitung von Prof. Dr. sc. nat. R. K. Dubey Role of Peroxisome Proliferator-Activated Receptor γ and Estrogen Receptors in Mediating the Anti-Mitogenic Actions of Phytoestrogens INAUGURAL-DISSERTATION zur Erlangung der Doktorwürde der Medizinischen Fakultät der Universität Zürich vorgelegt von Eva-Maria Boogen von Deutschland Genehmigt auf Antrag von Prof. Dr. med. B. Imthurn Zürich 2008