Dissociation between the magnitude of nuclear binding and the biopotency of glucocorticoids.
After 5 days of incubation with 10 nM tritiated dexamethasone, the amount of glucocorticoid displaceably-bound by the ACTH-secreting, glucocorticoid-responsive AtT-20 mouse pituitary tumor cell decreases by 70-80%. This decrease takes place in both the cytosolic and nuclear fractions. Although one might predict that there should be a decrease in agonist efficacy associated with this loss of nuclear binding, there was not; long-term incubations with dexamethasone revealed that the AtT-20 cells showed no tendency to resume secreting ACTH. Hence, although there was a dramatic decrease in the amount of nuclear-bound steroid, there was not a resulting decrease in the steroid's biopotency. These results suggest that the agonist-induced decrease in receptor content is either a means of removing redundant nuclear receptors, or a new, previously unrecognized, step in the mechanism of glucocorticoid hormone action.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D051379:Mice; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology*; D011987:Receptors, Steroid / Q000502:physiology*; D013997:Time Factors
D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone