Inhibition of the ACTH Adrenal Response to Stress by Treatment with Hydrocortisone, Prednisolone and Dexamethasone in the Rat

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Abstract
Adrenalectomized and 16 and 14 wk old intact rats were treated with different doses of the 3 glucocorticoids hydrocortisone, prednisolone and dexamethasone by gavage. The delayed feedback effect on plasma ACTH and cortiocosterone response to an ether stress were assessed. Almost complete suppression of corticosterone response 20 min after an ether stress and an ACTH suppression to 20% of control values 5 min after an ether stress were observed with 25 .mu.g of dexamethasone, 10 mg of prednisolone and 20 mg of hydrocortisone. Although percent inhibition of corticosterone and ACTH response to stress was comparable, a striking dissociation of the ACTH and corticosterone release was observed in terms of absolute concentrations. A mean ACTH concentration of 462 ng/l after 25 .mu.g of dexamethasone was measured together with a barley measurable corticosterone concentration of 3 .mu.g%. Similarly, after 10mg of prednisolone, the mean ACTH concentration was 404 ng/l, whilst the mean corticosterone concentration was 3 .mu.g%. This dissociation demonstrates that the corticosterone concentration on its own does not necessarily reflect the ACTH release. At 4 wk of age, the ACTH response to stress is more difficult to suppress than in adult animals. This is more obvious after adrenalectomy, where the excessive ACTH secretion was less inhibited by all glucocorticoids used. The time between the last steroid gaveage and stress must be considered. In 4 wk old animals the ACTH response 16 h after 12.5 .mu.g of dexamethasone was inhibited by 22%; 4 h after the same dexamethasone dose the inhibition was 85%. Under the experimental conditions used in rats degree and duration of feedback inhibition depend on the total steroid dose applied and on the regimen of drug administration. A dissociation between corticosterone and ACTH release is obvious. A wt-related potency ratio of feedback inhibition was 1:2:400-800 for hydrocortisone to prednisolone to dexamethasone.