Hill D J, Han V K
MRC Group in Fetal and Neonatal Health and Development, Lawson Research Institute, London, Ontario, Canada.
J Dev Physiol. 1991 Feb;15(2):91-104.
Embryonic and fetal growth is dependent on genetic factors and epigenetic factors such as peptide growth factors. We describe here the interactions of several peptide growth factors during the growth and function of two cell types, growth plate chondrocytes from the ovine fetus and astroglial cells from the newborn rat cerebral cortex. Isolated chondrocytes released two endogenous growth factors, basic fibroblast growth factor (bFGF) and insulin-like growth factor II (IGF II). Although the latter was released in greater abundance, as detected by radioimmunoassay, exogenous bFGF was more than a thousand fold more active as a mitogen. Insulin was also able to increase chondrocyte replication at physiological concentrations, and bFGF, insulin and IGFs were additive in their effects on DNA and protein synthesis. Transforming growth factor beta (TGF beta), which is abundant in bone, had little effect on chondrocyte DNA or total protein synthesis alone, but blocked the stimulatory actions of insulin and IGFs on these parameters. However, TGF beta when alone or in combination caused an increase in the collagen: non collagenous protein ratio of new proteins synthesized by chondrocytes. Adult rat brain is a rich source of IGF II, and both IGF I and II are present during neurogenesis and gliagenesis in the fetal and neonatal rat respectively. We have cultured astroglial cells isolated from neonatal rat cerebral cortex to examine the production and interaction of peptide growth factors during their growth. Isolated astroglial cells contained mRNAs encoding both IGF I and II but abundance was not regulated by other hormones or growth factors. Using affinity cross-linking we found that cultured cells also released two species of IGF binding protein (IGF-BP) of 33 kDa and 38 kDa. Northern blot analysis using homologous cDNA probes showed that astroglial cells expressed IGF-BP2 and BP3, but little BP1. Both IGF I and II were mitogenic for astroglial cells, as was insulin at physiologic concentrations. Exogenous IGF-BP2 was able to modulate the mitogenic actions of exogenous IGF I. These two very different cell models show many similarities of endogenous growth control. Both release IGFs and IGF-BPs which regulate mitogenic rate. In addition, in both insulin functions as a growth factor at physiologic concentrations. These findings suggest common principles governing embryonic and fetal growth and development. Studies have shown that fetal and neonatal growth is independent of regulation by classic hormones (e.g. growth hormones) synthesized by the mother or the fetus. It is believed that embryonic and fetal growth is controlled by two major mechanisms, namely, (i) the genetic factors as determined by the embryonic and fetal genome, and (ii) the epigenetic and environmental factors that alter the expression of the embryonic or fetal genome.(ABSTRACT TRUNCATED AT 400 WORDS)
胚胎和胎儿的生长依赖于遗传因素以及诸如肽生长因子等表观遗传因素。我们在此描述了几种肽生长因子在两种细胞类型（绵羊胎儿的生长板软骨细胞和新生大鼠大脑皮层的星形胶质细胞）的生长和功能过程中的相互作用。分离出的软骨细胞释放出两种内源性生长因子，即碱性成纤维细胞生长因子（bFGF）和胰岛素样生长因子II（IGF II）。尽管通过放射免疫测定法检测到后者释放量更大，但外源性bFGF作为有丝分裂原的活性要高出一千多倍。胰岛素在生理浓度下也能够增加软骨细胞的复制，并且bFGF、胰岛素和胰岛素样生长因子对DNA和蛋白质合成的作用具有相加性。在骨骼中大量存在的转化生长因子β（TGFβ），单独对软骨细胞DNA或总蛋白质合成几乎没有影响，但会阻断胰岛素和胰岛素样生长因子对这些参数的刺激作用。然而，单独或联合使用时，TGFβ会导致软骨细胞合成的新蛋白质中胶原蛋白与非胶原蛋白的比例增加。成年大鼠大脑是IGF II的丰富来源，并且IGF I和II分别在胎儿期和新生大鼠的神经发生和胶质发生过程中存在。我们培养了从新生大鼠大脑皮层分离出的星形胶质细胞，以研究肽生长因子在其生长过程中的产生和相互作用。分离出的星形胶质细胞含有编码IGF I和II的mRNA，但丰度不受其他激素或生长因子的调节。通过亲和交联我们发现，培养的细胞还释放出两种分子量分别为33 kDa和38 kDa的胰岛素样生长因子结合蛋白（IGF - BP）。使用同源cDNA探针进行的Northern印迹分析表明，星形胶质细胞表达IGF - BP2和BP3，但几乎不表达BP1。IGF I和II对星形胶质细胞都有促有丝分裂作用，胰岛素在生理浓度下也是如此。外源性IGF - BP2能够调节外源性IGF I的促有丝分裂作用。这两种截然不同的细胞模型显示出内源性生长控制方面的许多相似之处。两者都释放调节有丝分裂速率的胰岛素样生长因子和胰岛素样生长因子结合蛋白。此外，在这两种细胞中，胰岛素在生理浓度下起生长因子的作用。这些发现提示了支配胚胎和胎儿生长发育的共同原则。研究表明，胎儿和新生儿的生长独立于由母体或胎儿合成的经典激素（如生长激素）的调节。据信，胚胎和胎儿的生长受两种主要机制控制，即：（i）由胚胎和胎儿基因组决定的遗传因素，以及（ii）改变胚胎或胎儿基因组表达的表观遗传和环境因素。（摘要截短至400字）
