Expression of insulin-like growth factor I in transgenic mice with elevated levels of growth hormone is correlated with growth.
Expression of insulin-like growth factor I in transgenic mice with elevated levels of growth hormone is correlated with growth.
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DOI：
10.1210/endo-123-1-433
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发表时间：
1988-07
期刊：
影响因子：
4.8
通讯作者：
L. Mathews;R. Hammer;R. Brinster;R. Palmiter
中科院分区：
文献类型：
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作者：
L. Mathews;R. Hammer;R. Brinster;R. Palmiter
为了研究胰岛素样生长因子I （IGF-I）在介导GH促生长功能中的作用，我们在携带GH或GRF融合基因的转基因小鼠中检测了IGF-I的表达。由于生长激素的高水平异位表达，这些小鼠表现出生长增强，肝脏IGF-I mRNA水平和循环IGF-I水平均升高2倍。无论生长激素水平如何，出生时肝脏igf - 1 mRNA水平都很低；它们在出生后的发育过程中增加约10倍，并在出生后2周成为生长激素诱导型。循环igf - 1的个体发生是相似的。生长激素融合基因转基因小鼠在出生后3周开始加速生长，尽管至少在出生时血液中生长激素水平就很高。此外，小鼠垂体中内源性分泌gh的生长营养细胞在3周时数量正常，但在出生后4周无法检测到。由于IGF-I表达成为GH响应的时间略早于加速生长的开始和内源性GH消失的时间，我们得出结论，IGF-I直接参与GH信号的介导，并且IGF-I基因表达的延迟诱导至少部分地导致了其他GH响应事件的延迟发生。
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.