Gastrin

Endogenous Hormone

Gastrin is a peptide hormone produced by G-cells located mainly in the antrum of the stomach, with smaller amounts made in the duodenum. Its predominant circulating form in humans is a 17-amino-acid peptide known as G-17 (little gastrin), although a larger 34-amino-acid form (G-34, big gastrin) also exists; both share the biologically active C-terminal sequence that determines gastrin's effects. Gastrin is released in response to the arrival of food in the stomach — particularly proteins and peptides — as well as gastric distension and signals from the vagus nerve. Its central role is to stimulate the secretion of gastric acid, preparing the stomach to break down food and to defend against ingested pathogens. Gastrin raises stomach acid through both direct and indirect routes. It acts on the CCK2 receptor (also called the gastrin/CCK-B receptor), most importantly on enterochromaffin-like (ECL) cells in the stomach lining, prompting them to release histamine. That histamine in turn stimulates the acid-producing parietal cells, which is the dominant pathway; gastrin also acts on parietal cells more directly. Beyond acid secretion, gastrin has trophic (growth-promoting) effects on the gastric mucosa, helping to maintain the stomach lining. Acid secretion is normally kept in check by feedback: as stomach contents become more acidic, the hormone somatostatin is released and suppresses further gastrin secretion, forming a self-regulating loop. Gastrin's clinical importance is dramatically illustrated by Zollinger-Ellison syndrome, a condition caused by a gastrin-secreting tumor called a gastrinoma (often in the pancreas or duodenum). Unregulated gastrin release drives massive acid overproduction, leading to severe, recurrent, and often treatment-resistant peptic ulcers along with diarrhea. Management centers on powerful acid suppression with proton pump inhibitors (PPIs), while somatostatin analogs such as octreotide and lanreotide can be used to suppress hormone secretion from the tumor, and treatment of the underlying gastrinoma is pursued where possible. Because measuring gastrin is central to diagnosing this condition, gastrin physiology has direct diagnostic relevance. Gastrin is an endogenous hormone and is not sold or given as a drug in its natural form. However, a synthetic fragment reproducing gastrin's active C-terminus — pentagastrin — was historically used as a diagnostic agent to provoke gastric acid secretion and to stimulate other hormone responses. Gastrin is best understood alongside its counterpart secretin, its close relative cholecystokinin (with which it shares the CCK2 receptor), and its synthetic diagnostic analog pentagastrin, together forming a coherent picture of how the stomach regulates acid and how that regulation can go wrong.