Molecular Pharmacology, Vol 14, 478-489, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Regulation of Phenylethanolamine N-Methyltransferase Synthesis and Degradation

I. Regulation by Rat Adrenal Glucocorticoids

¹ Child Psychiatry Program, Department of Psychiatry and Behavioral Sciences, Stanford Universtiy School of Medicine, Stanford, California 94305

The steady-state levels of rat adrenal phenylethanolamine N-methyltransferase are under the control of adrenal glucocorticoids. Following hypophysectomy, enzyme levels fall dramatically; they can be restored to normal by the administration of adrenocorticotrophin or dexamethasone. The decline in enzyme levels after hypophysectomy is accompanied by a decrease in the number of immunotitratable enzyme molecules; dexamethasone treatment restores the immunochemically reactive transferase. The decrease in number of enzyme molecules after hypophysectomy is due to accelerated proteolysis; this is reversed by glucocorticoid administration. Phenylethanolamine N-methyltransferase from hypophysectomized rats is more vulnerable to proteolysis in vivo and to denaturation at 50° in vitro, suggesting that hypophysectomy causes fundamental changes in the overall stability of the enzyme.

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