Multiple-level caerulein control of the gene expression of secretory proteins in the rat pancreas.
Continuous intravenous infusion of caerulein (0.25 micrograms X kg-1 X h-1) has recently been reported [Schick, J., Kern, H. & Scheele, G. (1984) J. Cell Biol. 99, 1569-1574] to enhance significantly the synthesis of both trypsinogen and chymotrypsinogen and to decrease that of amylase in the rat pancreas. With a view to achieving a better understanding of the mechanisms underlying caerulein modulation of pancreatic gene expression, the relative levels of active mRNA corresponding to these proteins were determined in caerulein-stimulated animals and compared to those of controls infused with a 0.9% NaCl solution. For this purpose, the translation products synthesized in vitro in a rabbit reticulocyte lysate translation system were measured. Prolonged caerulein infusion had less pronounced effects on mRNA levels as determined by the relative synthesis of translation products than on individual secretory proteins. No changes in mRNA levels were observed during 6 h of hormonal stimulation, whereas a 7-fold increase in the ratio of trypsinogen to amylase synthesis was obtained previously. After 24 h of caerulein infusion, only a slight change in active mRNA coding for amylase (1.7-fold) and serine protease zymogens (1.4-fold) occurred as compared to 14-fold and 2-fold variations in the synthesis rates of the corresponding proteins. These findings indicate that caerulein exerts a predominantly translational control on the biosynthesis of pancreatic amylase, trypsinogen and chymotrypsinogen even after 24 h of hormonal stimulation. However, additional control at a transcriptional or post-transcriptional level (i.e. via messenger RNA stability) may well take place.
C
C
Wicker
A
A
Puigserver
U
U
Rausch
G
G
Scheele
H
H
Kern
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002108:Ceruletide / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000201:enzymology / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012156:Reticulocytes / Q000378:metabolism; D013997:Time Factors
D011506:Proteins; D012333:RNA, Messenger; D002108:Ceruletide; D004247:DNA; D000681:Amylases