Differential extraction of estradiol- and tamoxifen-receptor complexes from hypothalamic cell nuclei

These experiments compared nuclear estradiol- and tamoxifen-receptor complexes from brain by measuring the ability of a series of ionic agents and DNA intercalators to release estrogen receptors from hypothalamic cell nuclei following in vivo administration of the agonist or antagonist. Over the concentration ranges tested, intercalators released 50-80% of the total estrogen receptors from hypothalamic cell nuclei in a concentration-independent fashion whereas extraction of nuclear receptors by the ionic agents was concentration dependent. In general, brain cell nuclear estrogen receptors were extracted more easily by both ionic agents and intercalators following injections of tamoxifen than of estradiol. It was also found that the polyanion heparin releases a small population of nuclear estrogen receptors that are not extracted by 0.5 M KCl, suggesting the existence of KCl-resistant chromatin acceptor sites in hypothalamic nuclei. These data support the hypothesis that estrogen agonists and antagonists promote different conformational changes when they bind neural estrogen receptors, resulting in the formation of ligand-receptor complexes with different biological activity.