Elevated Levels of Insulin-Like Growth Factor (IGF)-I in Serum Rescue the Severe Growth Retardation of IGF-I Null Mice
Elevated Levels of Insulin-Like Growth Factor (IGF)-I in Serum Rescue the Severe Growth Retardation of IGF-I Null Mice
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DOI：
10.1210/en.2009-0272
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发表时间：
2009-09-01
期刊：
影响因子：
4.8
通讯作者：
LeRoith, Derek
中科院分区：
文献类型：
--
作者：
Wu, YingJie;Sun, Hui;LeRoith, Derek
IGF-I在生长发育中起着至关重要的作用，并以内分泌和自分泌/旁分泌的方式发挥作用。本研究的目的是阐明血清中高水平的IGF-I能否挽救IGF-I缺失小鼠的严重生长迟缓和器官发育及功能。为了解决这一问题，我们在IGF-I基因缺失小鼠的肝脏中过表达了一种大鼠IGF-I转基因基因。我们发现，在完全缺乏组织IGF-I的情况下，血清中IGF-I水平的升高可以支持青春期和青春期后正常的身体尺寸，但不足以完全支持女性生殖系统(明显表现为发情周期不规律、卵巢黄体发育不良、子宫腺数量减少和子宫内膜发育不良，所有这些都会导致怀孕次数和产仔数减少)。我们的结论是，决定器官生长和功能的大多数IGF-I的自分泌/旁分泌作用可以被高水平的内分泌IGF-I所补偿。然而，在小鼠中，完全代偿反应在发育后期明显，这表明自分泌/旁分泌IGF-I对新生儿发育至关重要。此外，我们发现组织IGF-I对于女性生殖系统的发育是必要的，并且不能通过血清IGF-I水平的升高来补偿。(内分泌学150：4395-4403,2009)
IGF-I plays a vital role in growth and development and acts in an endocrine and an autocrine/paracrine fashion. The purpose of the current study was to clarify whether elevated levels of IGF-I in serum can rescue the severe growth retardation and organ development and function of igf-I null mice. To address that, we overexpressed a rat igf-I transgene specifically in the liver of igf-I null mice. We found that in the total absence of tissue IGF-I, elevated levels of IGF-I in serum can support normal body size at puberty and after puberty but are insufficient to fully support the female reproductive system (evident by irregular estrous cycle, impaired development of ovarian corpus luteum, reduced number of uterine glands and endometrial hypoplasia, all leading to decreased number of pregnancies and litter size). We conclude that most autocrine/paracrine actions of IGF-I that determine organ growth and function can be compensated by elevated levels of endocrine IGF-I. However, in mice, full compensatory responses are evident later in development, suggesting that autocrine/paracrine IGF-I is critical for neonatal development. Furthermore, we show that tissue IGF-I is necessary for the development of the female reproductive system and cannot be compensated by elevated levels of serum IGF-I. (Endocrinology 150: 4395-4403, 2009)