A Centenary of Gastrointestinal Endocrinology

Gastrointestinal hormones are peptides released to circulation from endocrine cells as well as neurons in the gastrointestinal tract. More than 30 hormone genes are currently known to be expressed in the stomach and intestines, which makes the gut the largest endocrine organ in the body. Moreover, cell and molecular biology now makes it feasible to conceive gastrointestinal endocrinology under five general headings: 1) The structural homology groups the hormones into eight families, each of which is assumed to originate from a common ancestral gene; 2) the individual hormone gene often have multiple phenotypes due to alternative splicing of the primary transcript, tandem organization of the translational product or differentiated maturation of the prohormone. By a combination of these mechanisms, more than 100 different hormonally active peptides are released from the gastrointestinal tract; 3) in addition, gut hormone genes are also widely expressed outside the gut, some only in neurons and/or in endocrine cells, but others also in other extraintestinal cell-types; 4) the different cell types may express different hormonally active fragments of the same prohormone by variation in the cell-specific posttranslational processing. Finally, 5) endocrine cells, neurons, and spermatozoa display different cell-specific release of gut peptides, so the same peptide may act as a metabolic blood-borne hormone, as a neurotransmitter, as a long-acting growth factor, and as an acute fertility factor.