The endocrine gut

Abstract

The gut is the largest endocrine organ in the body, both in terms of size and number of endocrine cells and hormones produced. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract. In order to overview the many hormonal peptides, it may be feasible to conceive the hormones under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization, or cell-specific maturation of hormone precursors. By a combination of these mechanisms, more than 100 different hormonally active peptides are released from the gut. Gut hormone genes, however, are also widely expressed in cells outside the gut, some only in extraintestinal endocrine cells and neurons but others also in other cell types. The extraintestinal cells may synthesize different bioactive peptide fragments of the same prohormone due to cell-specific biosynthetic pathways. Moreover, endocrine cells, neurons, myocytes, cancer cells, and, for instance, spermatozoa release the peptides differentially (autocrine, endocrine, myocrine, neurocrine, paracrine, spermiocrine secretion, etc.), so the same peptide may act as a blood-borne hormone, a neurotransmitter, a local growth factor, or a fertility factor. The molecular targets of each bioactive peptide are specific receptors expressed in the cell membranes of the target cells. Also the target cells of gut hormones occur widespread outside the digestive tract.