Effects of estrogenic compounds on uterine function and the metabolic disorders in ArKO mice

• Applicant: Professor Dr. Günter Vollmer
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2006 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 17445828

In the recent years the western industrialised nations are increasingly confronted with diseases connected with prosperity, hypercaloric consumption of food, and a decrease of physical activity, particularly with adiposity and the metabolic syndrome. Prerequisite to an effective treatment and a chemical prevention is a much better understanding of the therewith involved pathophysiological alterations, such as the interaction between estrogen function and its impact on general metabolism in relation to the detrimental alterations in the metabolic syndrome. The ArKO mouse model provides a suitable experimental model which connects the symptoms of adiposity and the metabolic syndrome with estrogen deficiency. The long term goal of this project is to set the stage for a selective rescue of the metabolic or the reproductive phenotype of ArKO mice by estrogen-like substances exhibiting SERM-like activities. As the first aim of this application we propose the identification of a mechanistic link between estrogens and metabolism. On the basis of our key expertise we focus on the elucidation of the regulatory pathways in the uterus but also in the adipose tissue by investigating the responsiveness of the leptin/leptin receptor or the PPAR axis to estrogens, SERMs, and phytoestrogens. The knowledge of the molecular basis of the interaction of key regulatory pathways and the potential involvement of phytoestrogens will help to design novel strategies for prevention.

• DFG Programme: Research Grants
• Participating Person: Dr. Jannette Wober