BIOSYNTHESIS, PROCESSING & SECRETION OF NEUROPEPTIDES & PITUITARY PEPTIDE HORMONE

ACTHI、内啡肽、α - msh、加压素和催产素的生物合成，

The biosynthesis of ACTHI, endorphin, Alpha-MSH, vasopressin and oxytocin, was studied with emphasis on the enzymes involved in the proteolytic processing of the respective prohormones. A prohormone converting enzyme (PCE) which specifically cleaves at paired basic residues oif the endogenous prohormones (pro-opiomelanocortin, prooxytocin and pro-vasopressin) to the active hormones, has been purified from bovine pituitary intermediate and neural lobe secretory vesicles. Purified PCE from both lobes appears to be identical and has been characterized as a about 70,000 dalton glycoprotein. PCE exists in a soluble and membrane associated form and was found to cleave pro-insulin to insulin as well. A carboxypeptidase B-like enzyme and an aminopeptidase B-like enzyme which function to remove the basic residues from the C- and N-terminal, respectively, from the peptide hormone, following the action of PCE, have been found in intermediate lobe and neural lobe secretory vesicles. The aminopeptidase B-like enzyme has been partially purified and characterized as a greater than 75,000 dalton metallopeptidase. The regulation of biosynthesis of pro-opiomelanocortin (POMC) by dopamine and cAMP was studied in the toad pituitary intermediate lobe. Pharmacological analyses indicate that the toad intermediate lobe dopamine receptor is of the D2 category and negatively coupled to adenylate cyclase. Thus the dopamine acts, subsequent to binding to the receptor, by lowering the intracellular cAMP level which then results in a decrease in POMC synthesis in the tissue. The regulation of POMC biosynthesis was also studied in mice under hyperosmotic stress. Salt loading the animals for two days resulted in a 2-3 fold increase in POMC mRNA levels, POMC synthesis and processing and secretion of POMC derived peptides from the anterior pituitary. In contrast POMC mRNA levels, POMC synthesis and secretion of POMC derived peptides were decreased by 56% in the intermediate lobe.