The role of compartmentalization of epinephrine in the regulation of phenylethanolamine N-methyltransferase synthesis in rat adrenal medulla.

The mechanism of regulation of phenylethanolamine N-methyltransferase (PNMT) in rat adrenal medulla after hypophysectomy and dexamethasone treatment was studied. The activity, amounts, and rates of synthesis and degradation of PNMT were measured in explants of adrenal medullae from sham-operated, hypophysectomized, and hypophysectomized-dexamethasone-treated rats. The storage, uptake, and catabolism of [3H]epinephrine were also measured in these three groups to determine any alteration in the granular vs. extragranular compartmentalization of epinephrine induced by these procedures. In addition, the effect of epinephrine on the rate of the enzyme's synthesis and degradation in cultured explants of medullae was measured. The results indicate that the 40% decrease in the amount of PNMT 1 month after hypophysectomy is due to a 28% decrease in the specific rate of synthesis of this enzyme. Dexamethasone treatment restores both the rate of synthesis of the enzyme and the amount of this enzyme found in the tissue to control levels. Our studies show that there is a 73% increase in uptake of [3H]epinephrine into medullary explants from hypophysectomized rats compared to controls. Fifty-six percent of this [3H]epinephrine was converted to metabolites in both groups, indicating that hypophysectomy produced no change in the rate of catabolism. However, uptake of [3H] epinephrine into medullary storage granules from hypophysectomized rats was decreased by 50%. These studies on the uptake, storage, and catabolism indicate that hypophysectomy favors conditions that increase levels of extragranular epinephrine. This altered compartmentalization is reversed by dexamethasone treatment, which decreases the uptake and increases the binding of epinephrine. Epinephrine added to cultured tissue decreased the rate of biosynthesis of PNMT by 22%, an extent similar to that observed after hypophysectomy. It is concluded that the effect of hypophysectomy on this enzyme is mediated by epinephrine.