Insulin-like growth factor I is essential for postnatal growth in response to growth hormone
Insulin-like growth factor I is essential for postnatal growth in response to growth hormone
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DOI：
10.1210/en.140.11.5178
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发表时间：
1999-11-01
期刊：
影响因子：
4.8
通讯作者：
LeRoith, D
中科院分区：
文献类型：
--
作者：
Liu, JL;LeRoith, D
胰岛素样生长因子 I (IGF-I) 对于细胞生长和子宫内发育至关重要，而 IGF-I 和 GH 都是出生后生长所必需的。为了探索 GH 对身体生长的直接作用（独立于 IGF-I 产生）的可能性，我们研究了 GH 对 Cre/loxP 系统创建的 IGF-I 缺陷小鼠品系的影响。 IGF-I缺失小鼠出生时生长迟缓35%，并表现出青春期前后生长延迟，生长明显缓慢，并且未达到青春期。它们的成年体重约为野生型同伴的三分之一，体长约为野生型同伴的三分之二。在出生后第 14 天 (P14) 至 P56 之间注射重组人 GH（rhGH，3 mg/kg，每天两次，皮下）未能刺激其生长（按体重和长度测量）。相比之下，接受相同剂量rhGH的野生型小鼠从P21开始表现出加速生长，一直持续到P56，与用稀释剂处理的对照小鼠相比，此时它们的体重增加了30%，长度增加了12%。尽管缺乏生长反应，但 IGF-I 缺失小鼠肝脏中 GH 受体表达水平正常，并且响应 rhGH 治疗而增加肝脏 Jun B 表达和肝脏大小。我们的结果支持 IGF-I 在 GH 诱导的小鼠产后身体生长中发挥重要作用。
Insulin-like growth factor I(IGF-I) is essential for cell growth and intrauterine development while both IGF-I and GH are required for postnatal growth. To explore the possibility of direct GH action on body growth, independent of IGF-I production, we have studied the effects of GH in an IGF-I-deficient mouse line created by the Cre/loxP system. The IGF-I null mice are born with 35% growth retardation and show delayed onset of peripubertal growth, grow significantly slower, and do not attain puberty. Their adult body weight was approximately one third and body length about two thirds that of their wild-type Litter mates. Injection of recombinant human GH (rhGH, 3 mg/kg, twice daily, sc) between postnatal day 14 (P14) to P56 failed to stimulate their growth as measured as both body weight and length. In contrast, wild-type mice receiving the same doses of rhGH exhibited accelerated growth starting at P21 that continued until P56, when their body weight was increased by 30% and length by 12% compared with control mice treated with diluent. Despite the lack of response in growth, IGF-I null mice have normal levels of GH receptor expression in the liver and increased liver Jun B expression and liver size in response to rhGH treatment. Our results support an essential role for IGF-I in GH-induced postnatal body growth in mice.