Kar S, Chabot J G, Quirion R
Douglas Hospital Research Center, Verdun, Quebec, Canada.
J Comp Neurol. 1993 Jul 15;333(3):375-97. doi: 10.1002/cne.903330306.
Insulin-like growth factors I and II (IGF I and IGF II) and insulin itself, which are structurally related polypeptides, play an important role in regulating brain growth and development as well as in the maintenance of its normal functions during adulthood. In order to provide a substrate for the better understanding of the roles of these growth factors, we have investigated the anatomical distribution as well as the variation in the density of [125I]IGF I, [125I]IGF II, and [125I]insulin receptor binding sites in developing and adult rat brain by in vitro quantitative autoradiography. The distributional profile of [125I]IGF I, [125I]IGF II, and [125I]insulin receptor binding sites showed a widespread but selective regional localization throughout the brain at all stages of development. The neuroanatomic regions which exhibited relatively high density of binding sites with each of these radioligands include the olfactory bulb, cortex, hippocampus, choroid plexus, and cerebellum. However, in any given region, receptor binding sites for IGF I, IGF II, or insulin are concentrated in anatomically distinct areas. In the cerebellum, for example, [125I]IGF II receptor binding sites are concentrated in the granular cell layer, [125I]insulin binding sites are localized primarily in the molecular layer, whereas [125I]IGF I receptor binding sites are noted in relatively high amounts in granular as well as molecular cell layers. The apparent density of sites recognized by each radioligand also undergoes remarkable variation in most brain nuclei, being relatively high either during late embryonic (i.e., IGF I and IGF II) or early postnatal (i.e., insulin) stages and then declining gradually to adult levels around the third week of postnatal development. These results, taken together, suggest that each receptor-ligand system is regulated differently during development and thus may have different roles in the process of cellular growth, differentiation, and maintenance of the nervous system. Furthermore, the localization of [125I]IGF I, [125I]IGF II, and [125I]insulin receptor binding sites over a wide variety of physiologically distinct brain regions suggests possible involvement of these growth factors in a variety of functions associated with specific neuronal pathways.
胰岛素样生长因子I和II（IGF I和IGF II）以及胰岛素本身是结构相关的多肽，在调节脑生长发育以及成年期维持其正常功能方面发挥着重要作用。为了更好地理解这些生长因子的作用提供基础，我们通过体外定量放射自显影研究了发育中和成年大鼠脑中[125I]IGF I、[125I]IGF II和[125I]胰岛素受体结合位点的解剖分布以及密度变化。[125I]IGF I、[125I]IGF II和[125I]胰岛素受体结合位点的分布图谱显示，在发育的各个阶段，它们在整个大脑中广泛但有选择性地区域定位。与这些放射性配体中每一种结合位点密度相对较高的神经解剖区域包括嗅球、皮质、海马、脉络丛和小脑。然而，在任何给定区域，IGF I、IGF II或胰岛素的受体结合位点集中在解剖学上不同的区域。例如，在小脑中，[125I]IGF II受体结合位点集中在颗粒细胞层，[125I]胰岛素结合位点主要位于分子层，而[125I]IGF I受体结合位点在颗粒细胞层和分子细胞层中含量相对较高。在大多数脑核中，每种放射性配体识别的位点的表观密度也有显著变化，在胚胎后期（即IGF I和IGF II）或出生后早期（即胰岛素）阶段相对较高，然后在出生后发育第三周左右逐渐下降到成年水平。综合这些结果表明，每个受体-配体系统在发育过程中受到不同的调节，因此在细胞生长、分化和神经系统维持过程中可能具有不同的作用。此外，[125I]IGF I、[125I]IGF II和[125I]胰岛素受体结合位点在多种生理上不同的脑区的定位表明，这些生长因子可能参与了与特定神经元通路相关的多种功能。
