Reflections on the Discovery and Significance of Estrogen Receptor ß
Konrad F. Koehler,
Luisa A. Helguero,
Lars-Arne Haldosén,
Margaret Warner and
Jan-Åke Gustafsson
KaroBio AB (K.F.K.), Novum, SE-141 57 Huddinge, Sweden; and Department of BioSciences and Medical Nutrition (L.A.H., L.-A.H., M.W., J.-Å.G.), Karolinska Institutet, Novum, SE-141 57 Huddinge, Sweden
Correspondence: Address all correspondence and requests for reprints to: Jan-Åke Gustafsson, Department of BioSciences and Medical Nutrition, Karolinska Institutet, Novum, SE-141 57 Huddinge, Sweden. E-mail: jan-ake.gustafsson{at}mednut.ki.se
We have known for many years that estrogen is more than thefemale hormone. It is essential in the male gonads, and in bothsexes, estrogen has functions in the skeleton and central nervoussystem, on behavior, and in the cardiovascular and immune systems.An important aspect of the discovery of estrogen receptor (ER)ß is that the diverse functions of estrogen can nowbe divided into those mediated by ER and those mediated by ERß.Pharmacological exploitation of this division of the laborsof estrogen is facilitated by the ligand-binding specificityand selective tissue distribution of the two ERs. Because theligand binding domains of ER and ERß are significantlydifferent from each other, selective ligands can be (and havebeen) developed to target the estrogenic pathway that is malfunctioning,without interfering with the other estrogen-regulated pathways.Because of the absence of ERß from the adult pituitaryand endometrium, ERß agonists can be used to targetERß with no risk of adverse effects from chemicalcastration and uterine cancer. Some of the diseases in whichthere is hope that ERß agonists will be of benefitare prostate cancer, autoimmune diseases, colon cancer, malignanciesof the immune system, and neurodegeneration.
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