Estrogen binding in nuclear and cytosolic extracts from brain and pituitary of middle-aged female rats

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Estrogen binding was compared in brain and pituitary of long-term ovariectomized young and middle-aged (MA) female rats. Binding was quantified in both cytosolic and nuclear extracts to ascertain whether fractions of estrogen binding are altered in MA females. Estrogen binding detected in nuclear extracts from hypothalamus/preoptic area and anterior pituitary of MA females was significantly lower than levels detected in young females. In each case where an age-related decrease in nuclear estrogen binding was observed, an increased number of putative estrogen receptors was detected in the cytosolic extract. Therefore, the age-related decrease in nuclear estrogen binding did not appear to result from a simple decrease in total available cellular estrogen receptors. Rather these results suggest a decrease in the ability of putative estrogen receptors in aging females to remain tightly bound to nuclei after their isolation. The ability of estrogen receptor complexes from aging animals to bind to DNA was evaluated by DNA-cellulose chromatography in order to examine possible quantitative and qualitative differences in estrogen binding protein with age. The data did not indicate that the properties of estrogen receptors themselves changed with age. It is possible, therefore, that age-related alterations may interfere with the interaction between the estrogen receptor complex and the nucleus.