Liu J L, LeRoith D
Clinical Endocrinology Branch, The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1758, USA.
Endocrinology. 1999 Nov;140(11):5178-84. doi: 10.1210/endo.140.11.7151.
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.
胰岛素样生长因子I（IGF-I）对细胞生长和子宫内发育至关重要，而出生后生长则需要IGF-I和生长激素（GH）两者。为了探索GH独立于IGF-I产生而对身体生长产生直接作用的可能性，我们研究了GH在通过Cre/loxP系统创建的IGF-I缺陷小鼠品系中的作用。IGF-I基因敲除小鼠出生时生长迟缓35%，青春期前生长开始延迟，生长明显较慢，且未达到青春期。它们的成年体重约为野生型同窝小鼠的三分之一，体长约为三分之二。在出生后第14天（P14）至P56期间，每天皮下注射两次重组人生长激素（rhGH，3mg/kg），未能刺激它们的体重和体长增长。相比之下，接受相同剂量rhGH的野生型小鼠从P21开始生长加速，一直持续到P56，此时它们的体重比用稀释剂处理的对照小鼠增加了30%，体长增加了12%。尽管生长无反应，但IGF-I基因敲除小鼠肝脏中GH受体表达水平正常，且对rhGH治疗有反应，肝脏Jun B表达增加，肝脏大小增大。我们的结果支持IGF-I在小鼠出生后GH诱导的身体生长中起关键作用。
