A short negative feedback mechanism regulating corticotropin-releasing hormone release

The effect of ACTH administration on plasma CRH levels was studied. In five patients with Addison's disease and three patients with hypopituitarism, bolus iv injection of 0.25 and 0.5 mg ACTH-(1-24) reduced plasma CRH levels (that had become elevated 48 h after discontinuation of corticosteroid replacement) to near-normal levels at 30-60 min in a dose-dependent manner. Plasma immunoreactive beta-endorphin levels were similarly decreased in patients with Addison's disease. ACTH-(1-24) (0.25 and 0.5 mg) injection failed to inhibit plasma CRH levels in five normal subjects. Basal CRH release from the rat hypothalamic median eminence in vitro was inhibited by 0.22 and 2.2 nM ACTH-(1-24) and ACTH-(1-39) in a dose-dependent manner. These results suggest that in the absence of negative feedback control of ACTH secretion by glucocorticoids, ACTH can regulate its secretion by inhibition of hypothalamic CRH release.