Regulation of rat pineal hydroxyindole-O-methyltransferase: evidence of S-adenosylmethionine-mediated glucocorticoid control.
Rat pineal hydroxyindole-O-methyltransferase is controlled similarly to adrenal medullary phenylethanolamine N-methyltransferase. S-adenosylmethionine (SAM), the in vivo cofactor utilized by the enzyme to convert N-acetylserotonin to melatonin, protects this methyltransferase against tryptic proteolysis in vitro. Furthermore, in vivo studies suggest that the nucleoside itself is controlled by glucocorticoids. Hypophysectomy decreases hydroxyindole-O-methyltransferase levels as compared with control animals, while dexamethasone and SAM administration restore enzyme levels toward control values. In vitro proteolytic studies further demonstrate that, although N-acetylserotonin does not stabilize the enzyme against trypsinization, this substrate acts synergistically with SAM to confer greater stabilization than observed with SAM alone.
D000121:Acetylserotonin O-Methyltransferase / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000502:physiology*; D007016:Hypophysectomy; D066298:In Vitro Techniques; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D010870:Pineal Gland / Q000201:enzymology*; D051381:Rats; D012436:S-Adenosylmethionine / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000502:physiology; D014357:Trypsin / Q000378:metabolism
D005938:Glucocorticoids; D012701:Serotonin; D012436:S-Adenosylmethionine; D003907:Dexamethasone; D008780:Methyltransferases; D010625:Phenylethanolamine N-Methyltransferase; D000121:Acetylserotonin O-Methyltransferase; D014357:Trypsin; C006389:N-acetylserotonin