Peptide Hormone Biosynthesis — Recent Developments

Abstract

The biosynthesis of peptide hormones is now recognized to be a highly ordered series of events. These biosynthetic events can frequently be localized to a particular subcellular organelle (Fig.1). Each organelle will be discussed in turn, to emphasize the sequential nature of the maturation process. There will be frequent references to the synthesis and processing of the corticotropin/endorphin precursor within the pituitary. This multihormone precursor is often referred to as pro-opiomelanocortin (POMC). POMC is an interesting model to study, since many post-translational modifications are manifest within its maturation products. More intriguing is the fact that processing of this multihormone precursor is tissue specific. In the pars distalis or anterior lobe of the pituitary, ACTH, β-lipotropin (β-LPH), and an N-terminal or 16 K fragment are the major biosynthetic products. In the pars intermedia or intermediate lobe processing is more complete, and α-melanotropin (α-MSH), corticotropin-like intermediate lobe peptide (CLIP), γ-LPH, various forms of acetylated endorphin, γ-MSH, and a shortened N-terminal (16 K_1–49) fragment are the major products (Fig.2). More is known of this system than of many others, primarily because pituitary tissue is relatively easy to maintain in culture and lends itself well to classical pulse/chase biosynthetic experiments. Also the AtT-20 mouse pituitary tumour cell line has been an extremely useful and accurate model for anterior pituitary processing (for extensive reviews on this subject see Eipper and Mains 1980; Chrétien and Seidah 1981).