Hormones and the gastrointestinal tract

The gastrointestinal tract is the largest endocrine organ in the body, with its component cells dispersed along its length rather than being clustered in glands. Gut peptides integrate gastrointestinal function by regulating the actions of the epithelium, muscles, and nerves, affect the growth and development of the gut and—as has emerged comparatively recently—they also have a major role in appetite control. There is little evidence that many gut peptides act as hormones in a classical endocrine fashion: many are autocrine, regulating the function of the cell secreting them, or paracrine, influencing the behaviour of neighbouring cells of different types.

Many gut peptides have been described, including the following.

The gastrin–cholecystokinin family—gastrin, which stimulates gastric acid secretion and has a trophic effect on the gastric mucosa, and cholecystokinin, a postprandial satiety signal.

The secretin family—secretin, which stimulates production of watery, alkaline pancreatic juices; glucose-dependent insulinotropic peptide, which stimulates insulin release in response to a mixed meal; vasoactive intestinal peptide (VIP), a stimulator of small-intestinal and colonic enterocyte secretion of water and electrolytes.

Peptide products of preproglucagon—enteroglucagon, which may be important in gut adaptation; glucagon-like peptides 1 and 2 and oxyntomodulin, which induce satiety.

Peptide products of preproghrelin—ghrelin, which is the only hormone known to stimulate food intake; obestatin, whose physiological function is uncertain; and motilin, which accelerates intestinal transit.

Peptide tyrosine tyrosine (PYY), which slows intestinal transit, and neuropeptide Y, which is a potent vasoconstrictor, inhibits intestinal secretion, and depresses colonic motility.

Others—bombesin and the gastrin-releasing peptides; opioids; tachykinins; other gut peptides—neurotensin; somatostatin; chromogranin-derived peptides; and other peptide neurotransmitters.

Gastrointestinal disease may cause abnormalities of these gut peptides, e.g. (1) achlorhydria (from atrophic gastritis or drug-induced) causes elevation of circulating gastrin; (2) malabsorptive conditions are associated with a decrease in the amount of peptides produced in the affected region, and a compensatory elevation of other peptides.

Carcinoid syndrome

Carcinoid tumours are capable of producing serotonin (5-hydroxytryptamine; 5-HT). Carcinoid syndrome occurs in about 10% of patients with carcinoid tumours, usually midgut tumours that have metastasized to the liver. The cardinal feature is the carcinoid flush; other characteristic symptoms are secretory diarrhoea, cramping abdominal pain, nausea, and vomiting; and about 50% of patients have cardiac valve abnormalities. The diagnosis is made on the basis of elevated concentrations of 5-hydroxyindoleacetic acid in a 24-h urine collection, with localization by octreoscan (using radiolabelled octreotide), ultrasonography/CT, or endoscopy. Treatment is with simple antidiarrhoeal agents and octreotide, a long-acting, subcutaneously administered, somatostatin analogue. The 5-year survival rates for carcinoids (depending on location) are 33 to 98%.