Regulation of biogenic amine methyltransferases by glucocorticoids via s-adenosylmethionine and its metabolizing enzymes, methionine adenosyltransferase and s-adenosylhomocysteine hydrolase

Abstract

This report examines the possibility that glucocorticoids control the degradation of adrenal phenylethanolamine n-methyltransferase and pineal hydroxyindole O-methyltransferase by regualting endogenous concentrations of the cosubstrate, S-adenosylmethionine, via its metabolic enzymes, methionine adenosyltransferase and S-adenosylhomocysteine hydrolase. Assays for these latter enzymes were established and optimized in the adrenal and pineal glands. The effects of hypophysextomy and dexamethasone or ACTH treatment on these enzymes were monitored along with concomitant changes in methyltransferase activity. Hypophysectomy simultaneously decreases methionine adenosyltransferase and S-adenosylhomocysteine hydrolase activity in both tissues. Dexamethasone administration to hypophysectomized animals does not alter either methionine adenosyltransferase activity of S-adenosylhomocysteine hydrolase activity in the adrenal gland. However, it does increase S-adenosylhomocysteine hydrolase activity in the pineal gland. In contrast, ACTH administration restores both enzymes in the adrenal while being ineffective in the pineal. These results suggests that glucocorticoids may be regulating S-adenosylmethionine levels and methyltransferase activity via the metabolic enzymes, methionine adenosyltransferase and S-adenosylhomocysteine hydrolase, but that glucocoticoid control may be both tissue- and drug-specific.