AGE-RELATED-CHANGES IN PEPTIDE-23 PANCREATITIS-ASSOCIATED PROTEIN ANDPANCREATIC STONE PROTEIN REG GENE-EXPRESSION IN THE RAT AND REGULATION BY GROWTH HORMONE-RELEASING HORMONE

Peptide-23 is a 16-kilodalton protein secreted by rat pituitary cells that was first identified because it was regulated by GRF and somatost atin in a similar fashion to GH. Cloning of peptide-23 complementary D NA revealed that it is identical to pancreatitis-associated protein (P AP) and a member of the c-lectin gene family. We examined the expressi on of peptide-23/PAP and a structurally related protein, pancreatic st one protein (PSP/reg), in the rat gastrointestinal tract. Here we repo rt age-related changes in the expression and GRF regulation of peptide -23 Both peptide-23/PAP messenger RNA (mRNA) and PSP/reg mRNA were vir tually undetectable in the small intestine of newborn and 1- and 2-wee k-old rats. A dramatic increase in the expression of both genes was se en at the time of weaning in the third week postpartum. The abundance of both of these mRNA decreases after 3 and 6 months of age. Peptide-2 3/PAP mRNA is most abundant in the ileum, whereas PSP/reg is maximally expressed in the pancreas and duodenum. Human GRF analog pellets were implanted sc into adult male rats for 2 weeks to study the chronic ef fects of GRF on the expression of these genes. Both peptide-23/PAP and PSP/reg mRNA levels in duodenum and jejunum were increased in these r ats compared with levels in control rats. However, no increase in pept ide-23/PAP mRNA in response to GRF treatment was seen in the ileum, wh ere the level of expression of this gene is very high, and GRF had no effect on peptide-23/PSP expression in the heart, pituitary, or hypoth alamus, where expression is normally undetectable. In situ. hybridizat ion was used to localize peptide-23/PSP in the small intestine and pan creas of GRF-treated rats. An increase in peptide-23/PAP mRNA was rest ricted to acinar cells close to islets, whereas little expression was seen in acinar cells distant from islets, suggesting that either pepti de-23/PAP may have some paracrine action on the islets, or alternative ly, an islet-derived factor may function as a paracrine modulator of p eptide-23/PAP expression. These data demonstrate that GRF modulates pe ptide-23/PAP expression in the gastrointestinal tract in a similar fas hion to that previously reported for pituitary cells in primary cultur e.