IMMUNOHISTOCHEMICAL LOCALIZATION OF INSULIN-LIKE GROWTH FACTOR-II (IGF-II) AND IGF-BINDING PROTEIN-2 DURING DEVELOPMENT IN THE RAT-BRAIN

The insulin-like growth factors (IGF-I and IGF-II) are peptide growth factors with both growth-promoting and insulin-like activities. In the nervous system, the expression of both IGF-I and IGF-II messenger RNAs (mRNAs) is developmentally regulated, with IGF-I expression highest during puberty, and IGF-II levels peaking during the perinatal period. The IGFs interact with and are modulated by a group of six binding proteins, the IGF-binding proteins (IGFBP-1 to IGFBP-6). IGFBP-2 mRNA is most prevalent in the nervous system, where, like IGF-II, its expression correlates with a period of brain growth. In the current study, cells containing IGF-II and IGFBP-2 were identified within the developing nervous system of the rat on embryonic day 12 (E12), E14, E18, and postnatal day 1 and in the adult. IGF-LI immunoreactivity was detected within the mesenchymal core of the choroid plexus at all ages examined and was also observed in the developing leptomeninges. IGF-II appeared transiently in the central nervous system in presumptive glia of the hippocampus and medial basal hypothalamus and in a small population of neurons in the brain stem, IGFBP-2 was consistently observed in the epithelium of the choroid plexus as well as in the epithelia of the developing otic and olfactory placodes. While these results confirm the developmental expression of IGF-II and IGFBP-2 mRNA in the central nervous system, discrepancies exist between these data and those using molecular techniques. This may be due in part to differential sites of IGF-II and IGFBP-2 production compared to sites of action.