TY - JOUR T1 - Adrenocortical Control of the Biosynthesis of Epinephrine and Proteins in the Adrenal Medulla JF - Pharmacological Reviews JO - Pharmacol Rev SP - 411 LP - 426 VL - 24 IS - 2 AU - R. J. Wurtman AU - L. A. Pohorecky AU - B. S. Baliga Y1 - 1972/06/01 UR - http://pharmrev.aspetjournals.org/content/24/2/411.abstract N2 - The activity of phenylethanolamine-N-methyl transferase (PNMT) in the adrenal medulla declines markedly after hypophysectomy. Enzyme activity is restored if animals are treated with ACTH or very large doses of glucocorticoids, but not by "replacement" doses of glucocorticoids or by other pituitary or adrenal hormones. These observations indicate that basal levels of PNMT activity require that the medulla receive the very high concentrations of hydrocortisone or corticosterone that are available to it by virtue of its unique location within an envelope of adrenal cortex. The resotration by dexamethasone treatment of the PNMT activity in medullas of hypophysectomized animals is blocked by concurrent administration of actinomycin D or puromycin. Moreover, hypophysectomy is associated with decreases in the quantity of immunochemically assayable PNMT protein in the medulla and in the rate at which PNMT is synthesized from isotopically labeled amino acid precursors. These changes are also reversed by dexamethasone. Adrenomedullary polysomes are markedly disaggregated after hypophysectomy; however, polysome patterns revert to normal if animals are treated with ACTH or dexamethasone. These observations all suggest that glucocorticoids stimulate the synthesis not only of PNMT, but also of a wide variety of medullary proteins. The decrease in adrenal PNMT activity caused by hypophysectomy is associated with corresponding decreases in the mass of chromaffin cells and in the amounts of epinephrine stored in the adrenal medulla and secreted in response to physiological stimuli. After the induction of insulin hypoglycemia, adrenals of hypophysectomized dogs release considerably less epinephrine, and more norepinephrine, than those of control animals. Inasmuch as norepinephrine is far less potent than epinephrine in accelerating the breakdown of glycogen, the impairment in epinephrine synthesis caused by pituitary insufficiency may be related to the insulin sensitivity that often characterizes this disease. 1971, by The Williams & Wilkins Co. ER -