Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span
Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span
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DOI：
10.1210/en.2003-0374
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发表时间：
2003-09-01
期刊：
影响因子：
4.8
通讯作者：
Kopchick, JJ
中科院分区：
文献类型：
--
作者：
Coschigano, KT;Holland, AN;Kopchick, JJ
GH参与生长、代谢和细胞分化。为了研究这些作用，我们先前产生了两种不同的侏儒小鼠品系，一种表达GH拮抗剂（GHA），另一种具有破坏的GH受体和结合蛋白基因（GHR -/-）。本研究比较了两个具有相同遗传背景的矮秆系（C57 BL/6 J）。小鼠品系之间最显著的差异之一是断奶后的体重增加情况。随着时间的推移，GHA侏儒的体重逐渐接近对照，但GHR -/-侏儒的体重在整个分析期间保持较低。此外，空腹胰岛素和葡萄糖水平在GHR -/-小鼠中降低，但在GHA小鼠中正常。在两种小鼠系中，IGF-I和IGF结合蛋白3（IGFBP-3）水平均显著降低，但程度不同，但GHR -/-小鼠中IGFBP-1和-4水平降低，IGFBP-2水平升高，但GHA小鼠中未发生变化。最后，GHR -/-小鼠的寿命显着延长，但GHA侏儒保持不变。这些结果表明，GH信号传导的阻断程度可以导致显着不同的表型。
GH participates in growth, metabolism, and cellular differentiation. To study these roles, we previously generated two different dwarf mouse lines, one expressing a GH antagonist (GHA) and the other having a disrupted GH receptor and binding protein gene (GHR -/-). In this study we compared the two dwarf lines in the same genetic background (C57BL/6J). One of the most striking differences between the mouse lines was their weight gain profile after weaning. The weights of the GHA dwarfs gradually approached controls over time, but the weights of the GHR -/- dwarfs remained low throughout the analysis period. Additionally, fasting insulin and glucose levels were reduced in the GHR -/- mice but normal in the GHA mice. IGF-I and IGF binding protein 3 ( IGFBP-3) levels were significantly reduced, but by different degrees, in both mouse lines, but IGFBP-1 and -4 levels were reduced and IGFBP-2 levels increased in GHR -/- mice but unaltered in GHA mice. Finally, life span was significantly extended for the GHR -/- mice but remained unchanged for GHA dwarfs. These results suggest that the degree of blockade of GH signaling can lead to dramatically different phenotypes.