Studies of regulation of gastrin synthesis and post-translational processing by molecular biology approaches.

We have examined the regulation of gene expression and post-translational processing of progastrin by starvation and feeding in rats. An oligonucleotide complementary to rat preprogastrin cDNA was used in RNA blot and hybridization analysis to measure gastrin mRNA levels. A region-specific antibody raised against the predicted amino acid sequence of the carboxyl terminal extension of progastrin was used for quantitation of progastrin peptides. The effects of starvation and of refeeding on rat antral gastrin mRNA and pro-hormone peptide levels were examined in rats starved for 48 h and after refeeding with a solid meal. Antral gastrin mRNA concentrations decreased to a plateau level (30% of the nonstarved control) after 48 h of starvation. Immunoreactive gastrin concentration decreased threefold, but progastrin processing intermediates did not decrease significantly during fasting. Following refeeding, significant increases in antral mRNA level were detected in 1 h, and peak levels were reached by 2 h (more than two times higher than starved control). There was a rapid and significant decrease in progastrin immunoreactivity within 30 min, followed by a significant increase in gastrin immunoreactivity 2 h after refeeding. These data suggest that rapid increases of blood and tissue gastrin levels in response to food may be associated with increases in both gastrin gene expression and post-translational processing of progastrin.