Chief Cell

Reviewed by: BD Editors

Chief cells are enzyme-secreting cells of the stomach. They are found in the gastric glands and produce pepsinogen, the inactive precursor to pepsin, and gastric lipase. The enzymes produced by chief cells mix with hydrochloric acid and other secretions to produce gastric fluid, which is a vital component of protein and lipid digestion in the stomach.

Chief cells secrete pepsinogen and gastric lipase in the stomach
Chief cells are enzyme-producing cells in the stomach

What is a Chief Cell?

A gastric chief cell (AKA a zymogenic cell) is a type of epithelial cell located in the stomach lining. Its primary function is to synthesize and secrete pepsinogen; the inactive precursor to the enzyme pepsin, which is activated upon contact with hydrochloric acid. Chief cells of the stomach also produce the gastric lipase enzyme. Therefore, gastric chief cells play a central role in the digestion of dietary proteins and lipids in the stomach.

Location of Chief Cells

The mucosal layer of the stomach lining contains numerous gastric glands, each of which contains a variety of specialized cells. Each cell in the gastric gland secretes a component of gastric fluid, which is then released into the stomach.

The specialized cells of the gastric glands include chief cells (which secrete pepsinogen and gastric lipase), and parietal cells (which produce hydrochloric acid), along with mucus and hormone-secreting cells. These secretions combine to form gastric fluid, which initiates protein and lipid digestion in the stomach.

Chief cells are found in the gastric glands of the stomach
The gastric glands contain a variety of specialized cells

Structure and Function of Chief Cells

The primary function of a gastric chief cell is to produce pepsinogen (the inactive precursor to pepsin) and gastric lipase. Chief cells are highly adapted to keep up with the high protein synthesis rate required for enzyme secretion.

Pepsinogen Production

Pepsinogen is the inactive precursor to pepsin, a protease. It is produced and secreted by gastric chief cells and is activated upon contact with hydrochloric acid in the gastric fluid. Once activated, pepsin begins to digest proteins into smaller peptides and amino acids in the stomach.

Chief cells are the primary producers of pepsinogen in the body and contain abundant rough endoplasmic reticulum (RER) for protein synthesis. They also house lots of secretory granules (called zymogen granules), which store pepsinogen and other digestive enzymes until they are needed.

Chief cells contain abundant rough endoplasmic reticulum and secretory granules
Chief cells are highly adapted for protein synthesis

Gastric Lipase Production

Chief cells also produce gastric lipase, which helps to digest triglycerides into simple fatty acids, diglycerides, and monoglycerides. Like pepsinogen, gastric lipase is synthesized by the RER and stored in the secretory granules of chief cells.

Stimulation of Chief Cells

Digestive enzymes are stored inside the secretory vesicles of chief cells and are released in response to various stimuli. Low pH, the neurotransmitter acetylcholine, and the hormone gastrin are all known to stimulate gastric chief cells.


Gastric chief cells are stimulated by the neurotransmitter, acetylcholine
Acetylcholine is a neurotransmitter released by the vagus nerve

The first stage of digestion is the cephalic phase, in which the sight, thought, or smell of food stimulates the vagus nerve. The vagus nerve releases a type of neurotransmitter called acetylcholine, which triggers the release of pepsinogen from the gastric chief cells. Acetylcholine from the vagus nerve also triggers parietal cells to secrete hydrochloric acid, which converts the pepsinogen to the active enzyme, pepsin.


Gastrin is a gastrointestinal hormone released by G cells in the stomach and duodenum of the small intestine. G cells produce gastrin in response to several stimuli, including stretching of the stomach, high amino acid and peptide concentration, low pH, and vagus nerve stimulation. Gastrin triggers chief cells to secrete pepsinogen, and parietal cells to release hydrochloric acid.

The gastrointestinal hormone gastrin is released by G cells
G cells release gastrin to stimulate chief cells in the stomach

Low pH

The low pH conditions of the stomach also stimulate gastric chief cells. When the parietal cells secrete hydrochloric acid, the contents of the stomach become more acidic and chief cells are triggered to release pepsinogen. The pepsinogen is activated on contact with the hydrochloric acid, and protein digestion can begin.

Cite This Article

MLAAPAChicago Editors. “Chief Cell.” Biology Dictionary,, 09 Jul. 2021, Editors. (2021, July 09). Chief Cell. Retrieved from Editors. “Chief Cell.” Biology Dictionary., July 09, 2021.

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