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首页> 外文期刊>Endocrinology >The acid-labile subunit is required for full effects of exogenous growth hormone on growth and carbohydrate metabolism.
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The acid-labile subunit is required for full effects of exogenous growth hormone on growth and carbohydrate metabolism.

机译：酸不稳定的亚基是充分发挥外源性生长激素对生长和碳水化合物代谢的作用所必需的。

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摘要

Normal postnatal growth is dependent in part on overlapping actions of GH and IGF-I. These actions reflect GH stimulation of IGF-I production in liver and extrahepatic tissues, representing respectively the endocrine and autocrine/paracrine arms of the IGF system. Recent experiments in genetically modified mice show that each source of IGF-I can compensate for absence of the other but do not resolve their relative role in postnatal growth. In an effort to address this issue, we studied the GH responsiveness of mice harboring a null mutation of the acid-labile subunit (ALS). Null ALS mice have a substantial reduction in endocrine IGF-I but, unlike other models of plasma IGF-I deficiency, have no obvious additional endocrine defects. Wild type and null ALS mice of both sexes received daily sc injections of saline or recombinant bovine GH between d 35 and 63 of postnatal age. The GH-stimulated body weight gain of null ALS mice was reduced by more than 30% relative to wild type mice, irrespective of sex. Reductions in GH responsiveness were also seen for kidney and linear growth. Absence of ALS eliminated the ability of GH to increase plasma IGF-I despite intact GH-dependent stimulation of IGF-I expression in liver, adipose tissue, and skeletal muscle. GH treatment was also less efficient in antagonizing insulin action in null ALS mice. Overall, these results suggest that the GH effects mediated by endocrine IGF-I depends on ALS, and accordingly null ALS mice are less responsive to exogenous GH therapy.
机译：正常的出生后生长部分取决于GH和IGF-I的重叠作用。这些作用反映了GH刺激肝和肝外组织中IGF-I产生，分别代表IGF系统的内分泌和自分泌/旁分泌臂。最近在转基因小鼠中进行的实验表明，每种IGF-I来源都可以弥补其他来源的缺失，但不能解决它们在产后生长中的相对作用。为了解决这个问题，我们研究了具有酸不稳定亚基（ALS）无效突变的小鼠的GH反应性。无效的ALS小鼠的内分泌IGF-I明显降低，但与血浆IGF-I缺乏的其他模型不同，它没有明显的其他内分泌缺陷。雌雄同体的野生型和无效ALS小鼠在出生后第35至63天之间每天皮下注射盐水或重组牛GH。与野生型小鼠相比，不论性别，GH刺激的空ALS小鼠的体重增加都减少了30％以上。肾脏和线性生长的GH反应性也降低。尽管完全依赖GH刺激了肝脏，脂肪组织和骨骼肌中的IGF-I表达，但无ALS消除了GH增加血浆IGF-I的能力。 GH治疗在无效ALS小鼠中拮抗胰岛素作用的效率也较低。总体而言，这些结果表明由内分泌IGF-1介导的GH效应取决于ALS，因此，无效ALS小鼠对外源GH治疗的反应较弱。

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