Age-related changes in peptide-23/pancreatitis-associated protein and pancreatic 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 somatostatin in a similar fashion to GH. Cloning of peptide-23 complementary DNA revealed that it is identical to pancreatitis-associated protein (PAP) and a member of the c-lectin gene family. We examined the expression of peptide-23/PAP and a structurally related protein, pancreatic stone protein (PSP/reg), in the rat gastrointestinal tract. Here we report age-related changes in the expression and GRF regulation of peptide-23. Both peptide-23/PAP messenger RNA (mRNA) and PSP/reg mRNA were virtually undetectable in the small intestine of newborn and 1- and 2-week-old rats. A dramatic increase in the expression of both genes was seen 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-23/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 effects 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 rats compared with levels in control rats. However, no increase in peptide-23/PAP mRNA in response to GRF treatment was seen in the ileum, where 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 hypothalamus, where expression is normally undetectable. In situ hybridization was used to localize peptide-23/PSP in the small intestine and pancreas of GRF-treated rats. An increase in peptide-23/PAP mRNA was restricted to acinar cells close to islets, whereas little expression was seen in acinar cells distant from islets, suggesting that either peptide-23/PAP may have some paracrine action on the islets, or alternatively, an islet-derived factor may function as a paracrine modulator of peptide-23/PAP expression. These data demonstrate that GRF modulates peptide-23/PAP expression in the gastrointestinal tract in a similar fashion to that previously reported for pituitary cells in primary culture.
Chakraborty
C
C
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Katsumata
N
N
Myal
Y
Y
Schroedter
I C
IC
Brazeau
P
P
Murphy
L J
LJ
Shiu
R P
RP
Friesen
H G
HG
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D000951:Antigens, Neoplasm; D001483:Base Sequence; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D003001:Cloning, Molecular; D017931:DNA Primers; D004064:Digestive System / Q000254:growth & development / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006321:Heart / Q000254:growth & development; D007031:Hypothalamus / Q000254:growth & development / Q000378:metabolism*; D037102:Lectins / Q000096:biosynthesis; D037181:Lectins, C-Type; D051847:Lithostathine; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009928:Organ Specificity; D010179:Pancreas / Q000254:growth & development / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D010902:Pituitary Gland / Q000254:growth & development / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D017931:DNA Primers; D037102:Lectins; D037181:Lectins, C-Type; D051847:Lithostathine; D009419:Nerve Tissue Proteins; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger; C497616:Reg1a protein, rat; C000612144:Reg3b protein, rat; D013007:Growth Hormone-Releasing Hormone