Distribution of Insulin-Like Growth Factor 1 (IGF-1) and 2 (IGF-2) Receptors in the Hippocampal Formation of Rats and Mice

Abstract
Since the discovery of specific receptors in the brain for insulin-like growth factor-1 and 2 (IGF-1 and IGF-2), there has been an increased interest in the role of these peptides as neurotrophic factors and/or neuromodulators in the central nervous system. Receptors for IGF-1 and IGF-2 have been characterized in brain membrane homogenates1–6 and localized to specific brain regions utilizing in vitro receptor autoradiographic and immunological techniques7–14. Competitive binding and affinity cross-linking studies have demonstrated that IGFs bind to two distinct receptors. The IGF-1 (type 1) receptor is structurally similar to the insulin receptor, consisting of 2 extracellular alpha subunits and 2 transmembranous beta subunits (approximately 130 and 95 kDa respectively)15–17. The IGF-2 (type 2) receptor consists of a single chain glycoprotein of approximately 250 kDa, which also binds mannose-6-phosphate18–22. Radioligand binding studies have demonstrated crossreactivity of the IGFs and insulin at the receptor level. The type I IGF receptor has higher affinity for IGF-1 than IGF-2 and insulin, and the type II IGF receptor binds IGF-2 with considerably higher affinity than IGF-1, and does not recognize insulin2,23.

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