Dynamics of glucocorticoid receptor and induction of tyrosine aminotransferase in rat liver.
In order to better understand the role of glucocorticoid receptor in the hormonal action of glucocorticoid, depletion and replenishment of the cytoplasmic receptor and kinetics of induction of tyrosine aminotransferase (TAT) in rat liver were examined after administration of dexamethasone (Dex) and prednisolone. The extent of the receptor depletion and the duration of the depletion period were dose-dependent and were well correlated not only with the biological potency of the steroids administered but also with the kinetics of TAT induction. A linear relationship between the amount of depleted receptor and the kinetics of TAT induction was observed. Pretreatment of animals with a large dose of Dex reduced the response of TAT induction by Dex which was administered 24 h later. This seems to be attributable, at least in part, to the incomplete replenishment of the receptor and also to the increased rate of replenishment of the receptor. The reduced affinity of the partially replenished receptor to glucocorticoid might also participate in lowering the response to the second injection. In conclusion, depletion and replenishment of the cytoplasmic glucocorticoid receptor appeared to be directly responsible for the physiological action of glucocorticoid.
D000818:Animals; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D014444:Tyrosine Transaminase / Q000096:biosynthesis*
D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D003907:Dexamethasone; D011239:Prednisolone; D014444:Tyrosine Transaminase