Characterization of a Calf Hypothalamic Extract with Adrenocorticotropin-Releasing Properties: Evidence for a Central Nervous System Site for Corticosteroid Inhibition of Adrenocorticotropin Release

Abstract

ACTH secretion, as indicated by increments in plasma corticosterone concentration or by adrenal ascorbic acid depletion, was studied in rats. Histamino, laparotomy, serotonin, pitressin, synthetic arginine vasopressin, calf cerebral cortical extract, or calf hypothalamic extract was used as ACTH-releasing stimuli. Morphine inhibited ACTH release following all the stimuli except the hypothalamic extract. The extract was found to be free of significant ACTH contamination in assays of hypophysectomized rats. It is concluded that morphine does not impair ACTH release at the pituitary, and that the hypothalamic extract possesses a unique ACTH-releasing activity. Corticosterone, in amounts shown to be physiological, inhibited the secretion of ACTH following histamine or laparotomy, but did not affect the secretion of ACTH when it was provoked by pitressin or hypothalamic extract. The corticosteroid inhibition of ACTH release following histamine or laparotomy thus appears to occur in the central nervous system, and not in the anterior pituitary. A schema describing the functional localization of the various sites of action of stimulators and inhibitors of ACTH release based on these data is presented. Requirements for an in vivo assay of hypophysiotropic, ACTH-releasing neurohormones are summarized.