Rhoads R P, Greenwood P L, Bell A W, Boisclair Y R
Department of Animal Science, Cornell University, Ithaca, NY 14853-4801, USA.
J Anim Sci. 2000 Oct;78(10):2681-9. doi: 10.2527/2000.78102681x.
In sheep, perinatal maturation of the endocrine arm of the insulin-like growth factor (IGF) system is characterized by two developmental events. First, concentrations of circulating IGF-I increase rapidly after birth and become responsive to changes in nutrition and growth hormone (GH). Second, the liver initiates synthesis of a serum protein called the acidlabile subunit (ALS). The acid-labile subunit promotes the endocrine actions of IGF-I and -II by recruiting them to long-lived complexes of 150 kDa. In this study, we examined the effect of nutrition on hepatic expression of the ALS gene around the time of birth and later in life. Expression of genes encoding other components of the circulating IGF system was also measured. At d 130 of fetal life, fetuses suffering from chronic undernutrition caused by placental insufficiency had lower expression of the ALS and IGF-I genes than well-nourished fetuses, but they did not have any changes in the expression of the IGF-binding protein (IGFBP)-2 or IGFBP-3 genes. In early postnatal life, hepatic gene expression was analyzed between d 12 and 38 in lambs fed a milk replacer at levels sustaining weight gains of 150 or 337 g/d. The lower plane of nutrition decreased the expression of the ALS, IGF-I, and GH receptor genes and increased the expression of the IGFBP-2 gene; expression of the IGFBP-3 gene was not affected by nutrition at this stage of life. Finally, hepatic gene expression was measured in 3-mo-old lambs offered ad libitum levels of a balanced diet or of a diet limiting for both energy and protein. Although the rate of growth of the lambs fed the limiting diet was reduced by 38%, the only effect detected in hepatic gene expression was a ninefold increase in the abundance of IGFBP-2 mRNA. Overall, these results indicate that undernutrition during late fetal and early postnatal life delays hepatic expression of the ALS gene and final maturation of the endocrine IGF system.
在绵羊中，胰岛素样生长因子（IGF）系统内分泌臂的围产期成熟具有两个发育事件。首先，出生后循环中IGF-I的浓度迅速增加，并对营养和生长激素（GH）的变化产生反应。其次，肝脏开始合成一种名为酸不稳定亚基（ALS）的血清蛋白。酸不稳定亚基通过将IGF-I和-II募集到150 kDa的长寿复合物中来促进它们的内分泌作用。在本研究中，我们研究了营养对出生前后及生命后期肝脏ALS基因表达的影响。还测量了循环IGF系统其他成分编码基因的表达。在胎儿期第130天，因胎盘功能不全而遭受慢性营养不良的胎儿，其ALS和IGF-I基因的表达低于营养良好的胎儿，但IGF结合蛋白（IGFBP）-2或IGFBP-3基因的表达没有任何变化。在出生后早期，对体重增加维持在150或337 g/d水平的代乳粉喂养的羔羊在第12至38天之间进行肝脏基因表达分析。较低的营养水平降低了ALS、IGF-I和GH受体基因 的表达，并增加了IGFBP-2基因的表达；在生命的这个阶段，IGFBP-3基因的表达不受营养的影响。最后，在随意提供均衡饮食或能量和蛋白质均受限饮食的3月龄羔羊中测量肝脏基因表达。尽管喂养受限饮食的羔羊生长速度降低了38%，但在肝脏基因表达中检测到的唯一影响是IGFBP-2 mRNA丰度增加了9倍。总体而言，这些结果表明，胎儿后期和出生后早期的营养不良会延迟肝脏ALS基因的表达以及内分泌IGF系统的最终成熟。
