Gastrin is a peptide hormone that plays a central role in the digestive process by managing the highly acidic environment within the stomach. It functions as a chemical messenger, traveling through the bloodstream to initiate the necessary steps for breaking down ingested food. Understanding the action and regulation of this hormone is important for grasping the complex coordination that governs overall digestive health.
The Source and Structure of Gastrin
Gastrin is manufactured and released by specialized endocrine cells known as G cells, which are mainly situated in the antrum, the lower section of the stomach. G cells also appear in smaller numbers in the duodenum, the first part of the small intestine. As a peptide hormone, gastrin is a small protein chain secreted directly into the bloodstream to reach its target organs. It is initially synthesized as a precursor and then processed into multiple forms, such as the predominant circulating form known as gastrin-34, or “big gastrin.”
Primary Role in Gastric Acid Production
The primary function of gastrin is the robust stimulation of stomach acid secretion, preparing the digestive tract for incoming food. Once released, gastrin travels to the upper parts of the stomach, acting on cells in the gastric lining. It binds to receptors on the parietal cells, which are directly responsible for releasing hydrochloric acid (HCl). This binding stimulates the insertion of proton pumps into the cell membrane, which actively secrete hydrogen ions into the stomach cavity, drastically lowering the pH.
Gastrin also exerts a powerful indirect effect by stimulating enterochromaffin-like (ECL) cells. These cells release histamine, which enhances the acid-secreting response of the parietal cells. The resulting hydrochloric acid is necessary for converting the inactive enzyme pepsinogen into its active form, pepsin, which starts the breakdown of dietary proteins. The highly acidic environment also acts as a protective barrier, killing most bacteria and microorganisms ingested with food.
Beyond stimulating acid, gastrin also has a secondary, growth-promoting effect on the stomach lining. This trophic action supports the health and proliferation of the gastric mucosa, helping maintain the integrity of the stomach wall. Gastrin’s influence also extends to increasing the stomach’s muscle contractions, which aids in churning food and moving it toward the small intestine.
Regulation and Control of Gastrin Release
The release of gastrin is tightly controlled by a feedback system that ensures acid is produced only when needed. Multiple factors stimulate G cells to release the hormone, beginning even before food enters the stomach. The anticipation of eating, transmitted through the vagus nerve, primes the stomach for digestion. Once food arrives, the stretching of the stomach walls and the presence of partially digested proteins, particularly amino acids, act as strong direct stimuli for gastrin secretion.
The most important mechanism for controlling gastrin release is a negative feedback loop based on acidity. When the stomach pH drops below 3.0, the environment signals the G cells to slow down production. This inhibition is largely mediated by D cells, which are stimulated by the low pH to release the hormone somatostatin. Somatostatin acts locally to suppress the activity of the G cells, reducing gastrin levels and limiting acid production.
Clinical Relevance of Gastrin Levels
Abnormal gastrin levels can indicate significant underlying digestive or endocrine disorders. An excessive amount of gastrin in the bloodstream, known as hypergastrinemia, is a primary concern because it leads to persistent overproduction of gastric acid. The most significant cause of hypergastrinemia is Zollinger-Ellison syndrome (ZES), a rare condition caused by gastrin-secreting tumors called gastrinomas. These tumors, which usually form in the pancreas or duodenum, secrete gastrin continuously, overwhelming normal regulatory mechanisms. The resulting high acid levels cause severe peptic ulcer disease that is often refractory to standard treatment and can also lead to chronic diarrhea.
Fasting serum gastrin levels are checked when ZES is suspected, though results can sometimes overlap with more common conditions. Low stomach acidity (hypochlorhydria) from other causes, such as chronic inflammation or atrophy of the stomach lining, can also lead to high gastrin levels. In this scenario, the body attempts to compensate for the lack of acid by increasing gastrin release, making the hypergastrinemia a symptom of low acid, rather than the cause of high acid.