Chin E, Zhou J, Bondy C
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Endocrinology. 1992 Jun;130(6):3237-45. doi: 10.1210/endo.130.6.1375897.
The rat kidney is both a target of circulating insulin-like growth factor-I (IGF-I) and a site of local IGF-I production. In order to identify which renal structures produce IGF-I and the functionally related IGF binding protein 1 (IGFBP-1), and which structures are potential sites of circulating or endogenous renal IGF action, we have employed in situ hybridization to localize IGF-I, IGFBP-1, and IGF-I receptor messenger RNAs (mRNAs) in the rat kidney. The effects of hypophysectomy (Hx) and GH replacement on renal IGF-I, IGFBP-1, and IGF-I receptor gene expression have also been evaluated. IGF-I and IGFBP-1 mRNAs are both localized in the epithelial cells of medullary thick ascending limbs (TALs) of Henle's loops in the normal rat kidney. IGF-I receptor mRNA is also abundant in TALs, but, in addition, is distributed throughout the distal nephron and collecting duct, and in the glomerulus, with lowest levels found in proximal tubules. Hx and GH treatment had complex effects on patterns of renal IGF-I and IGFBP-1 gene expression. In general, Hx resulted in decreased IGF-I and increased IGFBP-1 mRNA levels, and GH treatment produced the opposite effects, while IGF-I receptor mRNA levels were not significantly effected by either treatment. However, the most dramatic effect produced by the interruption of the pituitary-renal axis was the demonstration of reciprocal changes in IGF-I vs. IGFBP-1 gene expression in individual kidneys and even in individual nephrons, suggesting a local interaction between IGF-I and IGFBP-1 in the regulation of their respective mRNA levels. Functional implications issuing from these anatomical relationships in renal patterns of IGF-I, IGFBP-1, and IGF-I receptor gene expression are that IGF-I, if secreted into the tubular lumen, possibly carried or modulated by IGFBP-1, may act on luminal TAL and downstream receptor sites. The specific physiological role of IGF-I produced in TALs is open to speculation. Glomerular IGF-I receptor sites, based on their localization upstream and distant from local sources of IGF-I production, are predicted to be targets for circulating IGFs.
大鼠肾脏既是循环胰岛素样生长因子-I（IGF-I）的作用靶点，也是局部IGF-I的产生部位。为了确定哪些肾脏结构产生IGF-I和功能相关的胰岛素样生长因子结合蛋白1（IGFBP-1），以及哪些结构是循环或内源性肾脏IGF作用的潜在部位，我们采用原位杂交技术在大鼠肾脏中定位IGF-I、IGFBP-1和IGF-I受体信使核糖核酸（mRNA）。还评估了垂体切除（Hx）和生长激素替代对肾脏IGF-I、IGFBP-1和IGF-I受体基因表达的影响。在正常大鼠肾脏中，IGF-I和IGFBP-1 mRNA均定位于髓袢升支粗段（TAL）的上皮细胞中。IGF-I受体mRNA在TAL中也很丰富，但除此之外，还分布于整个远端肾单位和集合管以及肾小球，在近端小管中含量最低。Hx和生长激素治疗对肾脏IGF-I和IGFBP-1基因表达模式有复杂的影响。一般来说，Hx导致IGF-I水平降低和IGFBP-1 mRNA水平升高，生长激素治疗则产生相反的效果，而两种治疗对IGF-I受体mRNA水平均无显著影响。然而，垂体-肾脏轴中断产生的最显著影响是，在单个肾脏甚至单个肾单位中，IGF-I与IGFBP-1基因表达呈现出相反的变化，这表明IGF-I和IGFBP-1在调节各自mRNA水平方面存在局部相互作用。这些肾脏中IGF-I、IGFBP-1和IGF-I受体基因表达模式的解剖学关系所产生的功能意义在于，如果IGF-I分泌到肾小管腔中，可能由IGFBP-1携带或调节，它可能作用于管腔TAL和下游受体位点。TAL中产生的IGF-I的具体生理作用尚有待推测。基于肾小球IGF-I受体位点定位于IGF-I产生的局部来源的上游且距离较远，预计它们是循环IGF的作用靶点。
