Interference with Feedback Inhibition of Adrenocorticotropin Release by Protein Binding of Corticosterone

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Abstract
The capacity of intravenous injections of unbound corticosterone to inhibit corticotropin (ACTH) release following histamine was demonstrated using 2 different indices for ACTH release: changes in plasma corticosterone concentration and changes In adrenal content of corticosterone. At a dose of 100 [mu]g/100 g BW histamine caused nearly maximal ACTH release, but the dose was not supramaximal. The administration of unbound corticoster -one Intravenously 15-60 sec. before the histamine impaired the release of ACTH ordinarily provoked by the histamine. However, if the corticosterone was injected in the presence of corticosterone-binding proteins of plasma, the steroid then failed to Impair ACTH release following the histamine stimulus. The corticosterone injections produced transients in plasma total corticosterone concentrations that exceeded the physiological maximum. Consequently, it is not certain that the impairment of the negative feedback action of corticosterone y its binding proteins is present at lower total corticosterone concentrations.