March 01, 2006
The Schering Stiftung invited experts from around the world to exchange their ideas and latest findings in the field of estrogen research at a scientific symposium entitled “Tissue-Specific Estrogen Action: Novel Mechanisms, Novel Ligands, Novel Therapies?” held in Berlin.
The aim of modern estrogen research is to understand which tissues and organ functions are most affected by estrogens, and which signal cascades mediate estrogen actions. The latest findings suggest that there might be a number of different signalling pathways, through which these hormones act upon the body. Understanding the signalling pathways is crucial for the development of tailored therapies. The ultimate goal is to activate beneficial estrogen actions only in specific tissues of the body, i.e. in the skeletal system as protection from osteoporosis.
The many different actions of estrogens were discussed by Australian molecular biologist Professor Evan Simpson of Prince Henry’s Institute of Medical Research, Clayton, Australia, at the Berlin symposium: “A lack of estrogen promotes obesity, leads to poorer blood-fat profiles and a loss of bone density.” In his studies Simpson looks at transgenic ARKO-mice, which cannot produce estrogens, due to mutations in the aromatase enzyme. The total absence lack of estrogens leads to severe imbalances in the the mouse hormone metabolism. Disruptions of fat metabolism, obesity, osteoporosis and complex disorders like the metabolic syndrome are only some of the effects. Similar effects are observed in humans lacking sufficient levels of estrogens. Administration of estrogens usually leads to markedly improved conditions in humans and mice alike. “Treatment with 17-ß-estradiol, one of the estrogens, probably enhances the ß-oxidation of body fat,” Simpson supposes.
The effects of estrogens on fat metabolism and the skeletal system are only a few of the many aspects from the vast field of estrogen research. Estrogens influence the female sexual organs, the brain, the prostate, the cardio-vascular system as well as the immune- and digestive systems. In recent decades, growing knowledge of the actions of estrogens within the human body has led to various new directions of research activity in the field.
“Meetings like this one are extremely important for all of us,” said co-organizer Professor Kenneth S. Korach from the National Institute of Environmental Health Sciences, North Carolina. “Questions by colleagues from other areas open up new perspectives into your own research. The extensive exchange of ideas helps in developing new approaches in research and therapy and really boosts the entire field of research. It also encourages international co-operations.” Apart from Kenneth Korach, speakers included other pioneers in estrogen research like Michael Mendelsohn of Tufts New England Medical Center, Boston, MA, Ellis Levin of Long Beach VA Medical Center, Benita and John Katzenellenbogen from the University of Illinois, as well as Frank Gannon from the European Molecular Biology Laboratory (EMBL), Heidelberg.
The workshop on tissue-specific estrogens actions was the first event in 2006 in the “Scientific Symposia” series organized by the Schering Stiftung. “We envision the symposia as think tanks for new ideas. We aim to broaden scientific horizons and encourage dialogue between scientists of different research areas and institutions,” said Dr. Monika Lessl, molecular biologist and director of the board of the Schering Stiftung, in her opening speech.
Estrogens also play an important role in cardiovascular diseases. The latest research results from this area were presented by Michael Mendelsohn from Tufts University, Boston, MA, and Jean-Francois Arnal from Toulouse, France. Their studies demonstrate the important role estrogen receptors play in vascular-endothelial and smooth muscle cells play, in protecting blood vessels against injury. Mendelsohn’s studies show the mechanisms of smooth muscle cell growth being specifically inhibited by estrogens. His French colleague, Jean-Francois Arnal, looked at the controversial role of estrogens in atherosclerotic plaque: Estrogens seem to protect blood vessels from the built up of plaque in the first place, however they can have adverse effects on already existing plaque. Cells of the immune system play a key role in this process, Arnal and his colleagues demonstrate.
Not only do estrogens act selectively upon different types of cells, they also cause different effects in males and females. Looking for successful therapies for both men and women, scientists are increasingly tackling the molecular mechanisms of estrogens and their effects on genes and cells. “Rapid signaling” at the cellular membrane and testing of novel estrogen-like binding partners, so-called ligands, have become some of the new focal points in this field. “Estrogen research is like a house with many doors, which can so far only be opened with one master key,” explained Professor Frank Gannon. “We are currently looking for this perfectly matching key that will open only the desirable doors.”
The results of the symposium will be published by the Springer publishing house and will be available through bookstores. The “Scientific Symposia” series of the Schering Stiftung will continue on May 10–12, 2006, with a workshop on “GPCRs: From Deorphanization to Lead Structure Identification.”
Dr. Ken Korach, National Institute of Environmental Health Science, USA
Dr. Tim Wintermantel, Gynecology & Andrology, Schering AG, Berlin
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