Cellular localization and regulation of gene expression for components of the insulin-like growth factor ternary binding protein complex.

Cellular localization and regulation of gene expression for components of the insulin-like growth factor ternary binding protein complex.
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胰岛素样生长因子三元结合蛋白复合物成分的细胞定位和基因表达调节。

DOI:
10.1210/endo.134.6.7515002
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发表时间:
1994
期刊:
影响因子:
4.8
通讯作者:
C. Bondy
C. Bondy
中科院分区:
医学2区
文献类型:
--
作者:
E. Chin;Jian Zhou;J. Dai;R. Baxter;C. Bondy

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胰岛素样生长因子(IGF)存在于循环中,主要作为包括IGF结合蛋白-3(IGFBP-3)和酸不稳定亚基(ALS)的高分子量复合物的一部分。本研究采用原位杂交技术研究这些因素在大鼠的细胞合成位点,并评估在发育过程中和垂体切除术和GH治疗后转录水平的变化。IGFBP-3转录本在出生时比ALS更丰富和广泛表达,但两者都存在于肝脏和肾脏中。肝脏IGFBP-3基因表达略有增加,而ALS在出生后的前几周急剧增加。IGFBP-3 mRNA集中在门静脉和窦内皮,但在肝细胞中未检测到,而ALS mRNA在肝细胞中弥漫表达,但在非实质细胞中未检测到。这两种转录本都位于肾皮质;然而,IGFBP-3 mRNA集中在间质细胞中,而ALS在近端小管上皮中表达。垂体切除导致肝ALS减少90%,IGFBP-3 mRNA水平降低约50%。ALS,但不是IGFBP-3,转录也减少了肾脏。GH受体mRNA在肝、肾中与ALS共表达,提示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都比ALS广泛得多的事实表明,IGFBP-3除了对三元复合物的贡献外还具有作用。我们还表明,IGFBP-3和ALS是由不同的肝细胞类型合成的解剖组织,可能有助于确保有效形成的三元复合物的血液通过窦状隙。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位点。
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.
内皮细胞表达胰岛素样生长因子结合蛋白 2 至 6。
DOI: 10.1210/mend.6.11.1282670
发表时间: 1992
期刊: Molecular endocrinology (Baltimore, Md.)
影响因子: --
作者:
Moser,DR;LoweJr,WL;Dake,BL;Booth,BA;Boes,M;Clemmons,DR;Bar,RS
通讯作者: Bar,RS