One ancestor, several peptides: Post-translational modifications of preproghrelin generate several peptides with antithetical effects

Preproghrelin is the polypeptide precursor of ghrelin. First discovered in gastric extract as a growth hormone releasing peptide and food intake modulator, it has more recently been revealed to have other physiological aspects. The fine molecular mechanisms of ghrelin biosynthesis show that this peptide is but one piece of a puzzle which contains many other peptides obtained from alternative splicing of the same gene or from extensive post-translational modifications. Recent developments have shown that pro-ghrelin cleavage generates another active peptide named obestatin with an intriguingly subtle but opposite physiological action to ghrelin. Noteworthy, and similar to ghrelin, which requires post-translational processing close to its amino terminus by acylation, the biological activity of the ghrelin-associated peptide obestatin also depends on modification, but by amidation at its carboxyl terminus. In this review we will summarize the steps which led to the identification of pre-proghrelin gene products and will examine the significance and perspectives of the different peptides generated from the same ancestor gene.