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Deacylcortivazol acts through glucocorticoid receptors

Authors
Journal
Journal of Steroid Biochemistry
0022-4731
Publisher
Elsevier
Publication Date
Volume
14
Issue
3
Identifiers
DOI: 10.1016/0022-4731(81)90136-9

Abstract

Abstract Deacylcortivazol contains a phenyl-pyrazole moiety fused to the 2–3 position of the basic glucocorticoid steroid nucleus. When incubated with the glucocorticoid sensitive human leukemic cell line CEM-C7 it was found to be 20–50 times more cytotoxic than dexamethasone. In the same cell line it was 25-fold more active than dexamethasone in the induction of glutamine synthetase. Using a whole cell binding assay to measure competition for glucocorticoid receptors deacylcortivazol was found to be 17 times more effective than dexamethasone in competing with [ 3H]-dexamethasone for binding to receptor. When clones selected for resistance to 10 −6M dexamethasone and containing defective glucocorticoid receptors were treated with deacylcortivazol, no effect on cell growth or glutamine synthetase activity was observed, demonstrating a common pathway for the two steroids.

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