DOWN-REGULATION OF IGF-I MESSENGER-RNA EXPRESSION DURING POSTNATAL PANCREATIC DEVELOPMENT AND OVEREXPRESSION AFTER SUBTOTAL PANCREATECTOMY AND ACUTE-PANCREATITIS IN THE RAT PANCREAS

Insulin-like growth factors (IGFs) are important peptides involved in the regulation of cell growth and differentiation in many tissues. The ontogeny of IGF-I was examined in pancreata from 19-day rat fetuses, newborns and 5-, 11-, 26- and 70-day-old rats. For the regeneration st udies two models were used: (i) 90% pancreatectomy was carried out and the rats were killed at 1, 2, 3 and 6 days after resection; (ii) acut e pancreatitis was induced with caerulein (12 mu g/body weight three t imes a day every 8 h for 2 days) and the rats were killed at 1, 2, 5, 7 and 9 days after the first injection. Total RNA was extracted by the guanidinium isothiocyanate method and Northern blots were performed u sing total RNA and labeled cRNA probes. Abundance of the different mRN A transcripts was estimated by densitometric scanning and normalized t o the abundance of 18S rRNA for each time point. Northern blot analysi s during ontogeny showed four (0.8-1.2, 1.9, 4.7 and 7.5 kb) major tra nscripts in the rat pancreas and liver. Total IGF-I mRNA was 40-fold h igher in the adult liver than in the adult pancreas. Moreover, in the liver, IGF-I mRNA levels were higher in the adult than in the fetus, w hereas in the pancreas, the highest levels were observed around birth. During the first 3 days after pancreatectomy, a peak of maximal expre ssion was observed after the second day. Densitometric analysis of eac h IGF-I mRNA species showed concomitant increases in all transcripts. After 6 days, all transcripts had returned to near-control values. IGF -I mRNA expression 2 days after pancreatectomy was 3.5-fold higher tha n in the newborn. During the first 2 days of pancreatitis induction, o verexpression of mRNA was observed, However, soon after the second day of caerulein treatment, the 7.5 kb transcripts remained elevated wher eas those of the others regressed toward control values. Our results s how that IGF-I mRNA is overexpressed in both models of pancreatic rege neration but downregulated in the normal adult pancreas.