Mathews L S, Hammer R E, Brinster R L, Palmiter R D
Department of Biochemistry, University of Washington, Seattle 98195.
Endocrinology. 1988 Jul;123(1):433-7. doi: 10.1210/endo-123-1-433.
To study the role of insulin-like growth factor I (IGF-I) in mediating the growth-promoting function of GH, IGF-I expression was assayed in transgenic mice carrying either GH or GRF fusion genes. These mice exhibit enhanced growth as a result of high level ectopic expression of GH and have 2-fold elevation of both hepatic IGF-I mRNA levels and circulating IGF-I levels. Hepatic IGF-I mRNA levels are low at birth regardless of GH levels; they increase approximately 10-fold during postnatal development and become GH inducible 2 weeks after birth. The ontogeny of circulating IGF-I is similar. Accelerated growth in transgenic mice with GH fusion genes commences 3 weeks after birth despite high circulating GH levels at least as early as birth. In addition, endogenous mouse GH-secreting somatotroph cells in the pituitary are present in normal numbers at 3 weeks, but are undetectable 4 weeks after birth. Because the time at which IGF-I expression becomes GH responsive slightly precedes both the initiation of accelerated growth and the time when endogenous GH disappears, we conclude that IGF-I is directly involved in mediating the GH signal and that delayed induction of IGF-I gene expression is responsible, at least in part, for the delayed onset of other GH-responsive events.
为研究胰岛素样生长因子I（IGF-I）在介导生长激素（GH）促生长功能中的作用，对携带GH或生长激素释放因子（GRF）融合基因的转基因小鼠的IGF-I表达进行了检测。这些小鼠由于GH的高水平异位表达而表现出生长增强，肝脏IGF-I mRNA水平和循环IGF-I水平均升高两倍。无论GH水平如何，出生时肝脏IGF-I mRNA水平都很低；在出生后发育过程中它们大约增加10倍，并在出生后2周变得对GH有诱导性。循环IGF-I的个体发生情况类似。携带GH融合基因的转基因小鼠尽管至少在出生时循环GH水平就很高，但出生3周后才开始加速生长。此外，垂体中内源性分泌小鼠GH的生长激素细胞在3周时数量正常，但出生后4周就检测不到了。由于IGF-I表达对GH产生反应的时间略早于加速生长的开始以及内源性GH消失的时间，我们得出结论，IGF-I直接参与介导GH信号，并且IGF-I基因表达的延迟诱导至少部分导致了其他GH反应性事件的延迟发生。
