Mapping of brain insulin and insulin-like growth factor receptor gene expression by in situ hybridization

Abstract

The insulin and insulin-like growth factor I (IGF-I) receptors are members of a distinct tyrosine kinase receptor family. In situ hybridization employing ribonucleotide probes was used to compare patterns of insulin and IGF-I receptor gene expression in serial rat brain sections. A striking redundancy in anatomical patterns for insulin and IGF receptor gene expression is seen in many brain regions from olfactory bulb through cerebellum. Both receptor mRNAs are highest and appear to be coexpressed in the neuron-dense granule cell layers of olfactory bulb, dentate gyrus, and cerebellar cortex and pyramidal cell layers of piriform cortex and Ammon's horn, with relatively little hybridization detected in white matter zones. Superimposed on this generalized pattern are distinct local regions of selective enhancement in gene expression for the insulin or IGF-I receptor. Insulin receptor mRNA is more highly concentrated in anterior thalamic and hypothalamic structures which may have access to circulating insulin. IGF-I receptor mRNA is more highly expressed in projection neurons of sensory and cerebellar relay centers where local IGF-I synthesis is also concentrated. The overlap in insulin and IGF-I receptor gene expression found in many brain regions suggests that hybrid insulin-IGF receptors may be expressed in these regions. In summary, the gene expression patterns revealed in this study suggest that the insulin and IGF receptors may be among the most abundant and ubiquitous of the brain tyrosine kinases.