Lund P K, Moats-Staats B M, Hynes M A, Simmons J G, Jansen M, D'Ercole A J, Van Wyk J J
J Biol Chem. 1986 Nov 5;261(31):14539-44.
Somatomedin-C or insulin-like growth factor I (Sm-C/IGF-I) and insulin-like growth factor II (IGF-II) have been implicated in the regulation of fetal growth and development. In the present study 32P-labeled complementary DNA probes encoding human and mouse Sm-C/IGF-I and human IGF-II were used in Northern blot hybridizations to analyse rat Sm-C/IGF-I and IGF-II mRNAs in poly(A+) RNAs from intestine, liver, lung, and brain of adult rats and fetal rats between day 14 and 17 of gestation. In fetal rats, all four tissues contained a major mRNA of 1.7 kilobases (kb) that hybridized with the human Sm-C/IGF-I cDNA and mRNAs of 7.5, 4.7, 1.7, and 1.2 kb that hybridized with the mouse Sm-C/IGF-I cDNA. Adult rat intestine, liver, and lung also contained these mRNAs but Sm-C/IGF-I mRNAs were not detected in adult rat brain. These findings provide direct support for prior observations that multiple tissues in the fetus synthesize immunoreactive Sm-C/IGF-I and imply a role for Sm-C/IGF-I in fetal development as well as postnatally. The abundance of a 7.5-kb Sm-C/IGF-I mRNA in poly(A+) RNAs from adult rat liver was 10-50-fold higher than in other adult rat tissues which provides further evidence that in the adult rat the liver is a major site of Sm-C/IGF-I synthesis and source of circulating Sm-C/IGF-I. Multiple IGF-II mRNAs of estimated sizes 4.7, 3.9, 2.2, 1.75, and 1.2 kb were observed in fetal rat intestine, liver, lung, and brain. The 4.7- and 3.9-kb mRNAs were the major hybridizing IGF-II mRNAs in all fetal tissues. Higher abundance of IGF-II mRNAs in rat fetal tissues compared with adult tissues supports prior hypotheses, based on serum IGF-II concentrations, that IGF-II is predominantly a fetal somatomedin. IGF-II mRNAs are present, however, in some poly(A+) RNAs from adult rat tissues. The brain was the only tissue in the adult rat where the 4.7- and 3.9-kb IGF-II mRNAs were consistently detected. Some samples of adult rat intestine contained the 4.7- and 3.9-kb IGF-II mRNAs and some samples of adult liver and lung contained the 4.7-kb mRNA. These findings suggest that a role for IGF-II in the adult rat, particularly in the central nervous system, cannot be excluded.
生长调节素C或胰岛素样生长因子I(Sm-C/IGF-I)以及胰岛素样生长因子II(IGF-II)被认为参与了胎儿的生长和发育调节。在本研究中,用编码人及小鼠Sm-C/IGF-I的32P标记互补DNA探针和人IGF-II探针进行Northern印迹杂交,以分析成年大鼠及妊娠第14至17天的胎鼠的肠、肝、肺和脑中多聚腺苷酸(poly(A+))RNA中的大鼠Sm-C/IGF-I和IGF-II mRNA。在胎鼠中,所有这四种组织都含有一种1.7千碱基(kb)的主要mRNA,它可与人Sm-C/IGF-I cDNA杂交,还有7.5、4.7、1.7和1.2 kb的mRNA,可与小鼠Sm-C/IGF-I cDNA杂交。成年大鼠的肠、肝和肺也含有这些mRNA,但在成年大鼠脑中未检测到Sm-C/IGF-I mRNA。这些发现为先前的观察结果提供了直接支持,即胎儿的多种组织可合成免疫反应性Sm-C/IGF-I,并暗示Sm-C/IGF-I在胎儿发育以及出生后均发挥作用。成年大鼠肝脏的poly(A+) RNA中7.5-kb Sm-C/IGF-I mRNA的丰度比成年大鼠的其他组织高10 - 50倍,这进一步证明在成年大鼠中肝脏是Sm-C/IGF-I合成的主要部位及循环Sm-C/IGF-I的来源。在胎鼠的肠、肝、肺和脑中观察到了估计大小分别为4.7、3.9、2.2、1.75和1.2 kb的多种IGF-II mRNA。4.7-kb和3.9-kb的mRNA是所有胎儿组织中主要的杂交IGF-II mRNA。与成年组织相比,大鼠胎儿组织中IGF-II mRNA丰度更高,这支持了基于血清IGF-II浓度的先前假设,即IGF-II主要是一种胎儿生长调节素。然而,成年大鼠组织的一些poly(A+) RNA中也存在IGF-II mRNA。脑是成年大鼠中唯一始终能检测到4.7-kb和3.9-kb IGF-II mRNA的组织。成年大鼠肠的一些样本含有4.7-kb和3.9-kb IGF-II mRNA,成年肝脏和肺的一些样本含有4.7-kb mRNA。这些发现表明不能排除IGF-II在成年大鼠中,尤其是在中枢神经系统中的作用。