Chin E, Zhou J, Dai J, Baxter R C, Bondy C A
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Endocrinology. 1994 Jun;134(6):2498-504. doi: 10.1210/endo.134.6.7515002.
Insulin-like growth factors (IGFs) are present in the circulation, largely as part of a high mol wt complex including IGF-binding protein-3 (IGFBP-3) and an acid-labile subunit (ALS). This study used in situ hybridization to investigate the cellular sites of synthesis of these factors in the rat and to evaluate changes in transcript levels during development and after hypophysectomy and GH treatment. IGFBP-3 transcripts are considerably more abundant and widely expressed than ALS at birth, but both are present in liver and kidney. Hepatic IGFBP-3 gene expression increases slightly, whereas ALS increases dramatically in the first few weeks after birth. IGFBP-3 mRNA is concentrated in portal venous and sinusoidal endothelium, but is not detected in hepatocytes, whereas ALS mRNA is diffusely expressed by hepatocytes, but is not detected in nonparenchymal cells. Both transcripts are localized in the renal cortex; however, IGFBP-3 mRNA is concentrated in interstitial cells, whereas ALS is expressed in proximal tubule epithelium. Hypophysectomy results in a 90% reduction in hepatic ALS and an approximately 50% decrease in IGFBP-3 mRNA level. ALS, but not IGFBP-3, transcripts were also reduced in the kidney. GH receptor mRNA is coexpressed with ALS in liver and kidney, suggesting that the effects of GH on ALS gene expression may be direct. In summary, the fact that IGFBP-3 gene expression is far more widespread than that of ALS in both spatial and temporal parameters suggests that IGFBP-3 has a role apart from contribution to the ternary complex. We have also shown that IGFBP-3 and ALS are synthesized by distinct hepatic cell types in an anatomical organization that may serve to ensure efficient formation of the ternary complex in the blood passing through the sinusoids. Finally, the present data suggest that regulation of ALS synthesis may be the primary site of GH regulation of ternary complex formation.
胰岛素样生长因子（IGFs）存在于循环系统中，主要以高分子量复合物的形式存在，该复合物包括胰岛素样生长因子结合蛋白-3（IGFBP-3）和一个酸性不稳定亚基（ALS）。本研究采用原位杂交技术，研究这些因子在大鼠体内的细胞合成部位，并评估其在发育过程中以及垂体切除和生长激素（GH）治疗后的转录水平变化。出生时，IGFBP-3转录本比ALS丰富得多且表达更广泛，但两者在肝脏和肾脏中均有表达。出生后的最初几周，肝脏中IGFBP-3基因表达略有增加，而ALS则显著增加。IGFBP-3 mRNA集中在门静脉和肝血窦内皮细胞中，但在肝细胞中未检测到，而ALS mRNA在肝细胞中广泛表达，但在非实质细胞中未检测到。两种转录本均定位于肾皮质；然而，IGFBP-3 mRNA集中在间质细胞中，而ALS在近端肾小管上皮细胞中表达。垂体切除导致肝脏中ALS减少90%，IGFBP-3 mRNA水平降低约50%。肾脏中ALS转录本也减少，但IGFBP-3未减少。GH受体mRNA在肝脏和肾脏中与ALS共表达，表明GH对ALS基因表达的影响可能是直接的。总之，IGFBP-3基因表达在空间和时间参数上比ALS广泛得多，这一事实表明IGFBP-3除了对三元复合物有贡献外，还具有其他作用。我们还表明，IGFBP-3和ALS由不同的肝细胞类型在解剖结构中合成，这可能有助于确保在流经肝血窦的血液中高效形成三元复合物。最后，目前的数据表明，ALS合成的调节可能是GH调节三元复合物形成的主要部位。
