STUDIES ON THE CONTROL OF CORTICOTROPHIN RELEASE

Abstract

Different substances known to occur in hypotbalamic nuclei and neurones were studied as ACTH releasers (adrenal ascorbic acid depletion method) in normal rats, in hypophysectomized rats, in hypophysectomized rats bearing a functional pituitary graft in the anterior chamber of the eye, and in rats in which the ACTH discharge following non-specific stimuli had been blocked by administration of 9-alpha-fluoro-hydrocortisone. Adrenaline, noradrenaline, acetylcholine, histamine, serotonin, Pitressin, Pitocin, lysine-vasopressin and synthetic oxytocin were found highly effective normal animals; Euler's substance P did not produce adrenal ascorbic acid depletion in normal rats. Acetylcholine, histamine, serotonin, Pitocin, synthetic oxytocin and adrenaline were ineffective when tested in the hypophysectomized-grafted animals; only Pitressin gave a significant fall in adrenal ascorbic acid concentration when directly applied to the grafted pituitary gland. In the steroid-blocked rats Pitressin, Pitocin and lysine-vasopressin were active as ACTH releasers when given through intravenous injections; the intracarotid injection of small doses of Pitressin was also active in the blocked rats; the other stressors were inhibited after steroid administration. These results are discussed in connection with the hypothesis that posterior pituitary principles could play a role in the physiological regulation of ACTH output.