Corticosterone regulates the level of hepatic glucocorticoid receptors in mice.
The effect of exogenous corticosterone on the level of mouse hepatic glucocorticoid receptor was monitored to ascertain whether agonist-induced glucocorticoid receptor regulation takes place in living animals as it does in isolated cell systems. Adrenalectomized male Swiss-Webster mice were given 1 mg of corticosterone ip and 24 hr later the glucocorticoid receptor binding capacity of a high-speed cytosolic extract of liver was measured. It was shown that at this time point the administered steroid had been totally cleared and thus, the decrease in binding capacity was a reflection of downregulation. Receptor binding capacity was decreased by 25%. Downregulation was not permanent; 48-72 hr after the injection receptor content returned to baseline. Multiple daily injections of corticosterone were no more effective at causing downregulation than a single injection. It is concluded that glucocorticoid agonists downregulate their own receptors in the glucocorticoid target organs of intact animals as they do in cloned cell models.
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Department of Medicine, Louisiana State University Medical Center, New Orleans 70112.
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D003907:Dexamethasone / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014222:Triamcinolone Acetonide / Q000378:metabolism
D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D014222:Triamcinolone Acetonide; D003345:Corticosterone