The intracellular binding of [3H]corticosterone and [3H]dexamethasone and their metabolites to macromolecules in rat liver cytosol was studied in vivo and in vitro. The macromolecules binding corticosterone and its metabolites were characterized as (a) a steroid conjugate binder (stokes radius 2.5 nm and sedimentation coefficient 4.1 S in high ionic strength; pI 8,7), (b) transcortin and (c) a glucocorticoid 'receptor'. Competition experiments indicated that corticosterone and dexamethasone bind to the same site of the glucocorticoid receptor molecule. Different Stokes radii between the corticosterone receptor and the dexamethasone receptor complexes (6.9 and 6.3 nm, respectively, in high ionic strength) indicate that the two ligands induce different conformations of the receptor protein. This may be of importance when explaining the qualitative differences between the cellular effects of natural and synthetic glucocorticoids. 5α dihydrocorticosterone, on the other hand, competed to a very limited extent with dexamethasone for binding sites on the receptor. An assay of the inductive effect on liver tyrosine aminotransferase and tryptophan oxygenase indicated that 5α dihydrocorticosterone was practically devoid of glucocorticoid activity. It is concluded that 5α dihydrocorticosterone probably does not act as the mediator of corticosterone action in rat liver.
|Original language||English (US)|
|Number of pages||8|
|Journal||European Journal of Biochemistry|
|State||Published - Feb 1977|
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