The Changing Concept of Gut Endocrinology

Gastrointestinal hormones are released from enteroendocrine cells in the digestive tract. More than 30 hormone genes are expressed, which make the gut the largest endocrine organ in the body. At present, it is feasible to conceive the hormones under 5 headings: the structural homology groups most hormones into 9 families, each of which is assumed to originate from a single gene. Today's hormone gene often has multiple phenotypes due to alternative splicing, tandem organization or differentiated maturation of the prohormone. By these mechanisms, more than 100 different hormonal peptides are released from the gut. Gut hormones are also widely expressed in extraintestinal cells. These cells may release different fragments of the same prohormone due to cell-specific processing pathways. Moreover, endocrine cells, immune cells, neurons, myocytes, kidney cells, sperm cells and cancer cells secrete gut peptides in different ways, so the same peptide may act for instance as a hormone, a neurotransmitter, a cytokine, a growth factor or a fertility factor. The targets of gastrointestinal hormones are specific G-protein coupled receptors that are expressed in the cell membrane all over the body. Thus, each gut hormone constitutes a regulatory system operating in the whole organism.