CHARACTERIZATION OF INSULIN-LIKE GROWTH FACTOR-I RECEPTORS IN THE MEDIAN-EMINENCE OF THE BRAIN AND THEIR MODULATION BY FOOD RESTRICTION
CHARACTERIZATION OF INSULIN-LIKE GROWTH FACTOR-I RECEPTORS IN THE MEDIAN-EMINENCE OF THE BRAIN AND THEIR MODULATION BY FOOD RESTRICTION
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DOI：
10.1210/endo-122-5-1940
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发表时间：
1988-05-01
期刊：
影响因子：
4.8
通讯作者：
BASKIN, DG
中科院分区：
文献类型：
--
作者：
BOHANNON, NJ;CORP, ES;BASKIN, DG
用冰冻大鼠脑切片，通过体外放射自显影术，测定了125I标记的[Thr59]胰岛素样生长因子I（IGF-I）在大鼠正中隆起的高亲和力结合位点。0.1 nM碘-[Thr59] IGF-I与脑切片的特异性结合在4 ℃下12小时达到最大值，24小时无变化。通过计算机数字图像分析放射自显影图像的密度测定表明，碘-[Thr59] IGF-I与正中隆起的特异性结合是可逆的。通过碘-[Thr59] IGF-I与未标记[Thr59] IGF-I、大鼠IGF-II（增殖刺激活性）和猪胰岛素的竞争，评价结合特异性。所有这些都被结合位点识别，但效力的等级顺序是[Thr59] IGF-I> IGF-II>胰岛素。生长抑素完全无效。此外，抗大鼠IGF-II受体的抗体不能阻断碘-[Thr59] IGF-I与正中隆起的结合。14天的食物限制（对照组食物摄入量的75%）导致6只食物限制大鼠的体重显著减轻和血浆免疫反应性IGF-I的减少（0.9 ± 0.01）。0.1 U/ml）与6个对照组的值（2.6. ±. 0.5 U/ml; P <0.001）。在限食大鼠中，正中隆起中125 I标记的[Thr59] IGF-I的结合显著增加，主要是由于正中隆起中碘-[Thr59] IGF-I结合位点浓度增加;结合亲和力（Kd）不变。结果表明，正中隆起具有I型IGF-I受体，其在与热量摄入减少和血浆IGF-I水平降低相关的代谢条件下变得更多。
High affinity binding sites for 125I-labeled [Thr59]insulin-like growth factor I (IGF-I) were measured in rat median eminence by in vitro autoradiography with slide-mounted sections of frozen rat brain. Specific binding of 0.1 nM iodo-[Thr59]IGF-I to brain slices reached maximum by 12 h at 4 C and was unchanged at 24 h. Densitometry by computer digital image analysis of autoradiographic images indicated that specific biding of iodo-[Thr59]IGF-I to the median eminence was reversible. The specificity of binding was evaluated with competition of iodo-[Thr59]IGF-I with unlabeled [Thr59]IGF-I, rat IGF-II (multiplication-stimulating activity), and porcine insulin. All were recognized by the binding site, but the rank order of potency was [Thr59]IGF-I > IGF-II > insulin. Somatostatin was completely ineffective. Further, an antibody against the rat IGF-II receptor did not block binding of iodo-[Thr59]IGF-I to the median eminence. Fourteen days of food restriction (75% of food intake of controls) resulted in significant weight loss and reduction of plasma immunoreactive IGF-I in six food-restricted rats (0.9 .+-. 0.1 U/ml) compared with values in six controls (2.6 .+-. 0.5 U/ml; P < 0.001). Binding of 125I-labeled [Thr59]IGF-I in the median eminence was significantly increased in the food-restricted rats, primarily due to an increase in the concentration of iodo-[Thr59]IGF-I-binding sites in the median eminence; the affinity (Kd) of binding was unchanged. The results indicate that the median eminence has type I IGF-I receptors, which become more numerous under metabolic conditions associated with decreased caloric intake and lowered plasma IGF-I levels.