Coordinate regulation of peptide acetyltransferase activity and proopiomelanocortin gene expression in the intermediate lobe of the rat pituitary.
Proopiomelanocortin (POMC) is posttranslationally processed in the intermediate lobe of the pituitary to both N-terminally acetylated and nonacetylated forms of alpha MSH and beta-endorphin (beta END). N-Acetylation substantially modifies the physiological responses produced by both peptides, suggesting that the activity of the peptide acetyltransferase, which posttranslationally acetylates beta END and des-acetyl-alpha MSH, may play an important role in defining the biological activity of the secretory products of the intermediate pituitary lobe. The present results demonstrate that peptide acetyltransferase activity is induced by treating rats chronically with the dopamine receptor antagonist haloperidol. Haloperidol administration produced parallel and essentially equivalent increases in acetyltransferase activity, POMC mRNA levels, and the content and secretion of POMC-derived peptides in the neurointermediate pituitary. Time-course and dose-response studies further demonstrated that acetyltransferase activity covaried with POMC mRNA and peptide levels. Chronic treatment with the dopamine receptor agonist bromocriptine had the opposite effects; it lowered acetyltransferase activity, POMC mRNA levels, and alpha MSH and beta END immunoreactivities. Subcellular fractionation showed that acetyltransferase activity was localized in three subcellular compartments corresponding in density to secretory vesicles, rough endoplasmic reticulum and Golgi apparatus, and cytosol. Haloperidol treatment significantly increased the specific activity of the secretory vesicle-associated acetyltransferase without affecting the specific activity of the enzymes present in the endoplasmic reticulum or cytosol. Together, these data indicate that peptide acetyltransferase activity and POMC biosynthesis are coregulated.
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002458:Cell Fractionation; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin; D008083:beta-Lipotropin / Q000378:metabolism
D004723:Endorphins; D012333:RNA, Messenger; D001971:Bromocriptine; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D009074:Melanocyte-Stimulating Hormones; D008083:beta-Lipotropin; D000123:Acetyltransferases; D006220:Haloperidol