Gastrin: old hormone, new functions

It is exactly a century since the gastric hormone gastrin was first described as a blood-borne regulator of gastric acid secretion. The identities of the main active forms of the hormone (the "classical gastrins") and their cellular and molecular sites of action in regulating acid secretion have all attracted sustained attention. However, recent work on peptides derived from the gastrin precursor that do not stimulate acid secretion ("non-classical gastrins"), together with studies on mice over-expressing the gene, or in which the gastrin gene has been deleted, suggest hitherto unsuspected roles in regulating cell proliferation, migration, and differentiation. Moreover, microarray and proteomic studies have identified previously unsuspected target genes of the classical gastrins. Some of the newer actions have implications for our understanding of the progression to cancer in oesophagus, stomach, pancreas and colon, all of which have recently been linked in one way or another to dysfunctional signalling involving products of the gastrin gene. The present review focuses on recent progress in understanding the biology of both classical and non-classical gastrins.