Control of Enzymatic Synthesis of Adrenaline in the Adrenal Medulla by Adrenal Cortical Steroids

Abstract

The activity of phenylethanolamine N-methyltransferase, the enzyme that catalyzes the N-methylation of noradrenaline to form adrenaline, falls following hypophysectomy. Enzyme activity can be restored by injections of adrenocorticotropic hormone (ACTH) or of dexamethasone, a potent synthetic glucocorticoid. The effect of ACTH on the adrenaline-forming enzyme is not direct, but involves stimulation of the release of endogenous glucocorticoids from the adrenal cortex. These steroids then act to elevate the activity of the transferase, which is principally localized in the adrenal medulla. The stimulation by glucocorticoids of phenylethanolamine N-methyltransferase activity can be blocked by the concurrent administration of puromycin or actinomycin D. Glucocorticoids do not stimulate the activity of other adrenal enzymes involved in catecholamine biosynthesis or metabolism, such as tyrosine hydroxylase, catechol O-methyltransferase, or monoamine oxidase.