Progastrin expression in mammalian pancreas.

Area of Science:

• Endocrinology
• Gastroenterology
• Comparative Physiology

Background:

• Gastrin is a key hormone regulating gastric acid secretion.
• Previous studies have faced challenges in detecting gastrin in normal pancreatic tissue.
• The expression and processing of progastrin in the pancreas remain incompletely understood.

Purpose of the Study:

• To investigate the expression and processing of progastrin in pancreatic tissue across different mammalian species and developmental stages.
• To elucidate the reasons behind the difficulties in detecting gastrin in normal pancreatic tissue.
• To determine the origin of gastrin-producing pancreatic tumors.

Main Methods:

• Utilized a library of sensitive, sequence-specific immunoassays for progastrin and its products.
• Analyzed fetal, neonatal, and adult pancreatic tissue from five mammalian species (cat, dog, human, pig, rat).
• Monitored extractions and chromatography before and after cleavage with processing-like enzymes.

Main Results:

• Progastrin and its products are expressed in the pancreas of all studied species, with concentrations ranging from 0.3 to 58.9 pmol/g.
• Processing of progastrin is age- and species-dependent, with fetal/neonatal pancreas showing higher processing to amidated gastrin than adult pancreas.
• Pancreatic processing is consistently less complete than in the adult antral mucosa, explaining prior detection failures.

Conclusions:

• The pancreas expresses progastrin and its products, with varying levels of processing influenced by age and species.
• Moderate expression and attenuated processing in the adult pancreas explain why gastrin was previously undetectable.
• Gastrin-producing pancreatic tumors originate from cells that normally express the gastrin gene, not ectopic sites.