The opiomelanotropinergic neuronal and endocrine systems.

Corticotrophin-like peptides in the rat pituitary.

The proopiomelanocortin (POMC) gene was most likely derived from an ancestral opioid-coding gene following the 1R chordate genome duplication event. During the radiation of the jawless fish, the POMC organization plan emerged multiple melanocortin sequences (α-MSH/ACTH and β-MSH) and a C-terminally extended opioid sequence (β-endorphin). Following the 2R genome duplication event, the γ-MSH sequence was gained. Among the jawed vertebrates, three distinct trends in the evolution of the POMC gene are apparent: the gain of the δ-MSH sequence (cartilaginous fish), the loss of the γ-MSH sequence (ray-finned fish), and the retention of the post 2R POMC organization plan (lobe-finned fish/tetrapods). POMC is synthesized in the pituitary gland and in neurons of the hypothalamus, where an array of posttranslational processing mechanisms, such as endoproteolytic cleavage and N-acetylation, generate distinct sets of end-products in these tissues. A striking feature of the melanocortin end-products is the rigorous conservation of the primary sequence of α-MSH and the first 25 amino acids of ACTH.

Evolution of POMC: origin, phylogeny, posttranslational processing, and the melanocortins.

The evolution of vertebrate corticotrophin and melanocyte stimulating hormone.

Evidence that N-acetylation regulates the behavioral activity of α-MSH in the rat and human central nervous system

A melanocyte-stimulating hormone (MSH) was isolated by gel filtration and ion-exchange chromatography from extracts of the pituitary glands of dogfish. Sequence studies were carried out on the hormone and its enzymically and chemically cleaved fragments. The sequence of the hormone, Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Met, shows that ten of its 11 residues are the same as ten of the 13 residues of mammalian α-MSH. About half of its molecules have the carboxyl group at the C-terminus free and about half are amidated; about a fifth have an extra tyrosine residue on the N-terminus, thereby making 11 residues the same as in mammalian α-MSH. Unlike the mammalian hormone, however, none of it was found to be N-acetylated.

P. J. Lowry

Papers

Purification and amino acid sequence of melanocyte-stimulating hormone from the dogfish Squalus acanthias.