PROCESSING OF PRO-OPIOMELANOCORTIN IN RAT, PORCINE AND HUMAN PITUITARIES

Publisher Summary This chapter discusses the processing of pro-opiomelanocortin in rat, porcine, and human pituitaries. The data presented in the chapter shows the initial synthesis of a pre-pro-opiomelanocortin molecule with a 26 residues signal peptide. Following excision of this segment by a signal peptidase, glycosylated forms of pro-opiomelanocortin are obtained. In the rat pars intermedia, these mature into two glycosylated N-terminal extensions, alpha-melanocyte-stimulating hormone (MSH) and beta-endorphin within 2 hours after the original synthesis. The metabolic stability of this N-terminal segment is further demonstrated after the successful purification of large amounts of unprocessed N-terminal 103 amino acids glycosylated products from both human and porcine pituitary pars distalis. In tumor situations such as the human Cushing tumor investigated the possible presence of a glycosylated adrenocorticotropic hormone (ACTH) is also hinted. It is not known yet what the biological function of this N-terminal extension is. The constancy of its gamma-MSH sequence between species and the large degree of homology within its first 79 residues would indicate that a hitherto unsuspected role can be anticipated.