Molecular Pharmacology, Vol 8, 511-520, Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics

Regulation of Adrenal Phenylethanolamine N-Methyltransferase Activity in Three Inbred Mouse Strains

¹ Department of Psychiatry, Stanford University School of Medicine, Stanford, California 94305

The regulation of phenylethanolamine N-methyltransferase (EC 2.1.1) has been studied in the adrenal glands of three inbred mouse strains: DBA/2J, C57BL/Ka, and CBA/J. Although the pituitary gland is involved in the regulation of enzyme activity in each strain, the mechanism of regulation of differs between strains. In the DBA/2J strain, both glucocorticoid and phenoxybenzamine administration as well as cold exposure were effective in increasing enzyme activity. These results suggest that the DBA/2J strain enzyme is under both glucocorticoid and neuronal control. In the C57BL/Ka strain, only cold exposure and ACTH were effective in phenylethanolamine N-methyltransferase induction. Exogenous glucocorticoid administration had no effect on enzyme activity. Hypophysectomy both reduced control enzyme levels and abolished the enzyme response to cold exposure. We therefore propose that ACTH exerts a regulatory effect on the enzyme without the mediation of adrenal glucocorticoids. No evidence for neuronal control of phenylethanolamine N-methyltransferase activity has been found in the C57BL/Ka strain. In the CBA/J strain, hypophysectomy virtually abolished the enzyme activity. Activity could be partially restored by ACTH or dexamethasone administration. Aminoglutethimide blocked the enzyme response to ACTH but not to dexamethasone, suggesting that the enzyme response to ACTH is mediated via glucocorticoids. No evidence for neuronal control of phenylethanolamine N-methyltransferase could be found in the CBA/J strain. The half-life of the enzyme was estimated to be 1 hr in the DBA strain, 3 hr in the C57BL/Ka strain, and 7 hr in the CBA/J strain. The rate of increase of enzyme activity following induction is 10-fold greater in the DBA/2J strain than in either the C57BL/Ka or CBA/J strains. These results suggest that there are qualitative as well as quantitative differences in genetic regulation of phenylethanolamine N-methyltransferase activity.

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