Role of growth hormone (GH) in liver regeneration
Role of growth hormone (GH) in liver regeneration
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DOI：
10.1210/en.2004-0655
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发表时间：
2004-10-01
期刊：
影响因子：
4.8
通讯作者：
Yakar, S
中科院分区：
文献类型：
--
作者：
Pennisi, PA;Kopchick, JJ;Yakar, S
肝脏再生是肝脏对损伤作出反应的一种基本机制。这一过程受内源性生长因子和细胞因子的调控，涉及完整器官内所有成熟细胞的增殖。为了了解GH/IGF-I轴在肝脏再生中的作用，我们对三组小鼠进行了部分肝切除术：GH拮抗剂（GHa）转基因小鼠，其中GH的作用被阻断；肝脏IGF-I缺陷小鼠，肝脏特异性缺乏IGF-I，也缺乏酸不稳定亚基（ALS； LID + ALSKO小鼠），其中IGF-I水平非常低，生长激素分泌增加；并控制老鼠。有趣的是，与对照组（100%）或LID + ALSKO小鼠（88%）相比，GHa转基因小鼠在部分肝切除术后的存活率（57%）显著降低。在对照组小鼠中，肝脏在4天后完全再生，而在LID + ALSKO小鼠中，肝脏再生需要7天。相比之下，在GHa小鼠中，4 d后肝脏再生仅达到原始肝脏质量的70%，此后没有改善。引人注目的是，肝切除术后36和48小时，对照组和LID + ALSKO小鼠的肝脏分别显示出强烈的5-溴-2'-脱氧尿嘧啶（BrdU）染色，而ga处理小鼠的肝脏BrdU染色显著降低。这些结果表明生长激素在肝脏再生中起关键作用，尽管它是否直接或间接起作用仍有待确定。
Liver regeneration is a fundamental mechanism by which the liver responds to injury. This process is regulated by endogenous growth factors and cytokines, and it involves proliferation of all mature cells that exist within the intact organ. To understand the role of the GH/IGF-I axis in liver regeneration, we performed partial hepatectomies in three groups of mice: GH antagonist (GHa) transgenic mice, in which the action of GH is blocked; liver IGF-I-deficient mice that lack IGF-I specifically in the liver and also lack the acid-labile subunit (ALS; LID + ALSKO mice), in which IGF-I levels are very low and GH secretion is increased; and control mice. Interestingly, the survival rate of GHa transgenic mice was dramatically reduced after partial hepatectomy (57%) compared with the survival rate of controls (100%) or LID + ALSKO mice (88%). In control mice, the liver was completely regenerated after 4 d, whereas liver regeneration required 7 d in LID + ALSKO mice. In contrast, in GHa mice, liver regeneration reached only 70% of the original liver mass after 4 d and did not improve thereafter. Strikingly, 36 and 48 h after hepatectomy, the livers of control and LID + ALSKO mice, respectively, exhibited intense 5-bromo-2'-deoxyuridine (BrdU) staining, whereas BrdU staining was dramatically decreased in the livers of GHa-treated mice. These results suggest that GH plays a critical role in liver regeneration, although whether it acts directly or indirectly remains to be determined.