Enhanced inhibition of estrogen receptor nuclear binding in the uterus of aged mice |
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| Authors: | S Belisle D Bellabarba J G Lehoux |
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| Affiliation: | 1. Departments of Obstetrics and Gynecology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Québec, Canada, J1H 5N4;2. Departments of Medicine, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Québec, Canada, J1H 5N4;3. Departments of Biochemistry, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebéc, Canada, J1H 5N4;1. Division of Endocrinology, University of California, Irvine, Irvine, CA 92717, USA;2. Tibor Rubin VAMC, Long Beach, Long Beach, CA 90822, USA;3. Departments of Medicine and Biological Chemistry, University of California, Irvine, Irvine, CA 92717, USA;1. Department of Cell Biology, Physiology and Immunology, School of Biology, University of Barcelona, Barcelona, 08028, Spain;2. Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, 08028, Spain;3. Department of Biochemistry and Molecular Biomedicine, School of Biology, University of Barcelona, Barcelona, 08028, Spain;4. Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, University of Barcelona, Barcelona, 08028, Spain;5. CIC bioGUNE, Basque Research Technology Alliance, BRTA, Bizkaia Technology Park, Derio, 48160, Spain;6. Instituto de Biomedicina de Valencia (IBV)-CSIC, Valencia, 46010, Spain;7. Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, 28029, Spain;8. Unidad de Biomedicina, (Unidad Asociada al CSIC), Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Universidad de Las Palmas, Gran Canaria, 35001, Spain;9. Area of Myocardial Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, 28029, Spain |
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| Abstract: | We have studied why uteri from aging mice show a decrease nuclear concentration of estrogen receptors (UER). While 50-60% of available cytosolic UER from ovariectomized (OVX) mice aged 4-8 months, upon physiochemical activation, are able to bind either to DNA-cellulose or nuclear suspensions from young animals, only 20-30% of comparable concentrations of cytosolic UER from mice aged 15-18 months did so under identical experimental conditions. Nuclear dilutions with uterine cytosolic fractions from estrogen treated OVX mice prior to determination of [3H] UER binding sites in nuclear suspensions decreased the number of nuclear ER sites in both age groups. However, we observed that cytosols from aged animals showed a greater ability to prevent [3H]E2 binding to nuclear sites when compared to young ones (inhibition index: 0.286 +/- 0.013 (SE) vs. 0.137 +/- 0.025, P less than 0.05). These changes occur independently of protein concentration and result from dilution of a specific endogenous inhibitor of [3H]E2 binding to nuclear sites. The significance of these observed differences is discussed. |
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