THE ONTOGENY OF INSULIN-LIKE GROWTH-FACTOR (IGF) AND IGF-BINDING PROTEIN GENE-EXPRESSION IN THE RAT PANCREAS

Insulin is important for optimal fetal and neonatal growth and development. Its continued availability is due, in part, to ongoing islet cell growth within the pancreas. IGFs and IGF-binding proteins (IGFBPs) have been implicated as paracrine regulators of islet cell growth within the developing pancreas. The purpose of this study was to determine whether the intact rat pancreas expresses mRNAs for IGF-I, IGF-II and IGFBPs, and how these might change with development. Liver was studied as a control tissue. Pancreas and liver were taken from fetal rats at 20-22 days of gestation, from postnatal rats at 1-21 days and from adult animals, and mRNAs for IGFs-I and -II and IGFBPs-1 to -6 were detected by Northern blot hybridization. The amount of IGF-II mRNA was greatest in the liver and pancreas of the fetal rat, and declined in both tissues during the neonatal period. Conversely, IGF-I mRNA levels were low but detectable in fetal life, and rose to adult levels within 2 weeks of birth. Both IGFBP-1 and IGFBP-2 mRNAs were present in fetal rat liver, increasing in amount over the first week of life, and declining in the adult. However, within the pancreas, IGFBP-1 mRNA was undetectable and IGFBP-2 mRNA was very low in the fetus and neonate. Both IGFBP-1 and IGFBP-2 mRNAs transiently appeared in the pancreas between postnatal weeks 2 and 3 and declined in the adult. IGFBP-3 and IGFBP-4 mRNAs were detected in both the liver and pancreas throughout the developmental period studied. IGFBP-3 mRNA increased in amount immediately following birth, while the quantity of IGFBP-4 mRNA increased sharply in liver from postnatal day 21, but declined in the pancreas. mRNA for IGFBP-5 or -6 was undetectable in either tissue. The results show that both IGF-I and IGF-II are expressed by rat pancreas from at least 20 days of gestation, the latter being predominant in fetal life and the former during postnatal development. In addition, at least four IGFBP mRNAs (IGFBPs-1, -2, -3 and -4) were expressed within the pancreas with distinct developmental patterns. IGFBP-3 and -4 were predominant in the fetal and neonatal periods, while increased expression of IGFBPs-1 and -2 occurred 2-3 weeks after birth. The ontogeny of IGFBP mRNA expression in pancreas differed from that in liver. The temporal and spatially specific pattern of IGF and IGFBP gene expression within the developing pancreas supports a paracrine role for the IGF-IGFBP axis during pancreatic development in the rat.