Discrete early changes in cellular subpopulations of rat uterine and anterior pituitary estrogen receptors in response to acute exposure to exogenous estradiol.
Distribution of estrogen receptors among ligand-occupied and unoccupied species in cytosolic and nuclear subcellular compartments has been analyzed as an acute response to administration of 5 micrograms of estradiol in adult female rats. Patterns of anterior pituitary and uterine receptor turnover were monitored at intervals over a 5-h period, using either intact or 2-weeks ovariectomized animals. In terms of total cellular receptor content, initial levels were higher in castrate animals, but rapidly fell to intact levels within an hour following estradiol injection. Cycloheximide given shortly before estradiol had no effect on total pituitary receptor patterns, but appeared to result in an elevation in total uterine receptor content at early intervals. Unoccupied cytosol receptors were rapidly depleted and, with the exception of castrate pituitary samples, showed some replenishment within 5 h, all of which was cycloheximide-sensitive. Initially, occupied cytosol receptors were low in intact rats, but were present at levels approaching those of the unoccupied cytosol receptor forms in the ovariectomized rat tissues. Occupied cytosol receptor levels fluctuated in response to estradiol. Subpopulations of nuclear receptors, especially the unoccupied species, showed significant tissue specificity. In the uterus, unoccupied nuclear forms were initially present in high amounts, and the levels did not change in response to estradiol administration. In the pituitary, the levels of these receptors rose and subsequently fell over the 5-h interval. Cycloheximide conferred a similar biphasic response to estradiol upon the otherwise insensitive unoccupied nuclear forms of the uterus. Occupied nuclear receptors turned over completely during the 5-h study interval, with the kinetics being faster in the castrate than the intact tissues. Cycloheximide affected occupied nuclear forms of the uterus only, dramatically increasing their levels in response to estrogen and causing prolonged retention in the castrate animal model. Collectively, the cycloheximide effects on this system are consistent with early estrogen induction or stimulation of a protein which inhibits accumulation of occupied or unoccupied receptor species within the nucleus. This re-examination of all forms of cellular estrogen receptors as they fluctuate acutely in response to exogenous estrogen has revealed several heretofore undetected responses which must be incorporated into the overall scheme of early estrogen action.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D051381:Rats; D011959:Receptors, Estradiol / Q000187:drug effects / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism*
D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D004958:Estradiol; D003513:Cycloheximide