Steroid structure and nuclear translocation of glucocorticoid receptors in intact atT-20 mouse pituitary tumor cells

Abstract

Both natural and synthetic glucocorticoids suppress corticotropin biosynthesis by AtT-20 mouse pituitary tumor cells, but their individual potencies in doing so are not clearly related to cytosol receptor affinity alone. This discrepancy may be partially explained by observations from this laboratory showing that glucocorticoid agonists vary in the efficiency with which they cause nuclear translocation of the glucocorticoid-receptor complex in the intact cell. The studies described in this paper are the result of our attempts to determine under in vivo conditions whether the varying abilities of several glucocorticoid agonists to cause nuclear translocation could be correlated with their ability to activate the receptor. Accordingly, the extent of nuclear binding and the proportion of occupied receptor which was activated was determined after incubation of intact AtT-20 cells with four labeled glucocorticoids. The percentage of bound receptor in the nuclear compartment for each steroid was 38 ± 2.6, 33 ± 2.3, 25 ± 2.2, and 22 ± 1.9 for triamcinolone acetonide, dexamethasone, prednisolone and corticosterone, respectively. Determination of the total amount of activated receptor within the cell (nuclear receptor + activated cytosol receptor) revealed that there was a linear correlation between the extent of nuclear binding caused by each steroid and the proportion of activated receptor. We conclude that activation occurs in vivo, is related to steroid structure, and determines the extent of nuclear translocation.