Ocrant I, Valentino K L, Eng L F, Hintz R L, Wilson D M, Rosenfeld R G
Department of Pediatrics, Stanford University, California 94305.
Endocrinology. 1988 Aug;123(2):1023-34. doi: 10.1210/endo-123-2-1023.
The description of the cellular localization of insulin-like growth factor (IGF) receptors in the central nervous system (CNS) remains incomplete, as do the descriptions of changes in their characteristics with respect to different developmental stages. We, therefore, performed affinity labeling studies in microsomal membrane preparations of adult and fetal rat brain and liver tissues with [125I]IGF-I and [125I]IGF-II. These studies demonstrated tissue- and developmental stage-specific structural variants of type I receptor alpha-subunits as well as type II receptors. The adult rat brain type I alpha-subunit had an apparent mol wt (Mr) of 127,000, whereas those of adult and fetal rat liver measured 140,000. Fetal rat brain microsomes, however, had two types of type I receptor alpha-subunits measuring 130,000 and 120,000 Mr. The larger subunit from fetal brain consistently migrated at an apparent Mr of 3,000, greater than subunits from adult brain. Both type I and II receptors were more abundant in fetal liver and brain than in adult tissues. Affinity labeling was also performed directly to monolayers of cultured fetal brain neurons and newborn astrocytes. These studies detected both type I and II receptors on the surfaces of both types of cells. However, only the high Mr (140,000) form of the type I alpha-subunit was detected in cultured CNS cells, suggesting that expression of low Mr variant receptors is altered in vitro. Type II receptors were demonstrated by immunohistochemistry in adult rat hypothalamic neurons. However, the majority of neurons did not react with type II receptor antibody. This finding implies that only a minority of hypothalamic neurons are capable of responding to IGF-II via type II receptors. On the other hand, all astrocytes had striking type II receptor immunoreactivity. This signifies a more general biological role for this receptor in astrocytes compared with neurons. These results suggest that different tissue-, developmental stage-, and cell-specific processes are mediated by IGF receptors and suggests new directions in which to explore potential biological actions for these receptor-ligand systems in the CNS.
胰岛素样生长因子（IGF）受体在中枢神经系统（CNS）中的细胞定位描述仍不完整，其特性随不同发育阶段的变化描述也同样如此。因此，我们用[125I]IGF-I和[125I]IGF-II对成年和胎鼠脑及肝组织的微粒体膜制剂进行了亲和标记研究。这些研究证明了I型受体α亚基以及II型受体的组织和发育阶段特异性结构变体。成年大鼠脑I型α亚基的表观分子量（Mr）为127,000，而成年和胎鼠肝的则为140,000。然而，胎鼠脑微粒体有两种I型受体α亚基，分子量分别为130,000和120,000 Mr。胎脑的较大亚基始终以比成年脑亚基大3,000的表观Mr迁移。I型和II型受体在胎肝和脑中都比在成年组织中更丰富。还对培养的胎脑神经元和新生星形胶质细胞单层进行了直接亲和标记。这些研究在两种类型细胞的表面都检测到了I型和II型受体。然而，在培养的中枢神经系统细胞中仅检测到高Mr（140,000）形式的I型α亚基，这表明低Mr变体受体的表达在体外发生了改变。通过免疫组织化学在成年大鼠下丘脑神经元中证实了II型受体。然而，大多数神经元不与II型受体抗体反应。这一发现意味着只有少数下丘脑神经元能够通过II型受体对IGF-II作出反应。另一方面，所有星形胶质细胞都有明显的II型受体免疫反应性。这表明该受体在星形胶质细胞中比在神经元中具有更普遍的生物学作用。这些结果表明，IGF受体介导了不同的组织、发育阶段和细胞特异性过程，并为探索这些受体-配体系统在中枢神经系统中的潜在生物学作用指明了新方向。
