EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-4 AND PROTEIN-5 MESSENGER-RNAS IN ADULT-RAT FOREBRAIN

Accumulating evidence indicates that the insulin-like growth factors ( IGFs) can act as neurotrophic factors. A family of at least six IGF bi nding proteins (IGFBPs) has been characterized. The IGFBPs prolong the half-life of IGFs in plasma and may modulate IGF action in a cell- or tissue-specific fashion. Two recently characterized IGFBPs, IGFBP-4 a nd -5, have been shown by northern blot hybridization to be expressed in rat brain, but their cellular sites of synthesis are poorly charact erized, Because IGFBP-4 and IGFBP-5 could potentially modulate IGF act ions in the brain, we used in situ hybridization histochemistry and S- 35-labeled IGFBP-4 and IGFBP-5 riboprobes to localize sites of IGFBP-4 and -5 mRNA expression in adult rat brain. The two IGFBP mRNAs are ab undantly expressed within discrete regions of brain. The expression pa tterns of the two genes are largely nonoverlapping. Notably, IGFBP-4 m RNA is highly expressed within hippocampal and cortical areas, whereas IGFBP-5 mRNA is not detected above background in these areas. Within the hippocampus, abundant IGFBP-4 mRNA expression is detected in pyram idal neurons of the subfields of Ammon's horn and the subiculum and in the granule cell layer of the anterior hippocampal continuation. In t he cortex, IGFBP-4 mRNA is widely expressed in most areas and layers. In contrast, IGFBP-5, but not IGFBP-4, mRNA is detected within thalami c nuclei, leptomeninges, and perivascular sheaths. The distinct expres sion patterns of IGFBP-4 and -5 mRNAs within the brain suggest that th ese IGFBPs may modulate paracrine/autocrine actions of the IGFs in dis crete brain regions or compartmentalization of the IGFs within the bra in. (C) 1994 Wiley-Liss, Inc.