Ontogeny of somatomedin during development in the mouse. Serum concentrations, molecular forms, binding proteins, and tissue receptors.
Ontogeny of somatomedin during development in the mouse. Serum concentrations, molecular forms, binding proteins, and tissue receptors.
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小鼠发育过程中生长调节素的个体发育。
DOI：
10.1016/0012-1606(80)90071-8
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发表时间：
1980
影响因子：
2.7
通讯作者：
Underwood,LE
中科院分区：
文献类型：
--
作者：
D'Ercole,AJ;Underwood,LE
本研究的目的是评估在胎儿和出生后发育过程中生长调节素的血清浓度和分子形式的个体发生，并确定生长调节素-C在不同发育阶段的血清结合蛋白的变化。胚胎、胎盘和蜕膜小鼠组织具有生长调节素受体，这一发现表明生长调节素在胎儿生长中发挥作用，并可能在维持妊娠中发挥作用。使用高度特异性的异源放射免疫测定法（RIA）和对生长调节素（而非生长调节素-C）的影响更敏感的低特异性膜结合试验（MBA）测定血清生长调节素-C。通过显示遗传生长激素缺陷小鼠和垂体切除小鼠的血清浓度降低，并通过生长激素治疗增加，对小鼠血清的测定进行了验证。与人一样，RIA仅测量小鼠血清中存在的一部分生长调节素-C。生长调节素的这种“掩盖”归因于血清结合蛋白的存在，并通过用酸处理血清样品来校正。通过RIA和MBA，血清生长调节素浓度在胎儿和新生小鼠中较低，出生后第4周开始升高，并在7周龄时达到成年值。成年小鼠血清在Sephacryl 200上的色谱图与人血清中观察到的色谱图相似：免疫反应性物质在表观分子量为140，000和30，000 - 40，000时洗脱。125 I标记的生长调节素C与血清组分结合的洗脱曲线与内源性活性模式几乎相同。与人血清一样，酸化小鼠血清中的生长调节素-C以较低分子量洗脱，与胰岛素和纯化的生长调节素-C一致。母体血清生长调节素在妊娠后半期下降，此时胎盘催乳素水平升高。沿着生长调节素含量的绝对下降是生长调节素结合蛋白上不饱和位点的出现。这些发现是出乎意料的，无法解释的，因为生长调节素在人类妊娠后期升高，几条证据表明胎盘催乳素有能力刺激生长调节素的产生。我们以前已经提出了证据表明，外植体的多个胎鼠组织合成生长调节素C。本研究表明，免疫反应生长调节素-C在胎鼠血清中的份额与以前报道的小鼠肝脏外植体获得的媒体相同的特性。生长调节素的作用似乎主要在其产生部位或附近发挥，循环水平并不能反映生长调节素C对胎儿生长的重要性。虽然阐明生长调节素-C和生长调节素结合蛋白的血清含量和分子形式的显着的发育变化可能是必不可少的澄清生长调节素对胎儿生长的作用，证明生长调节素刺激胎儿生长将在很大程度上取决于其对胎儿组织的生物学作用的研究。
The purpose of this study was to assess the ontogeny of serum concentrations and molecular forms of somatomedin during fetal and postnatal development and to define the changes in serum binding proteins for somatomedin-C during various stages of development. The finding that fetal, placental, and decidual mouse tissues possess receptors for somatomedin suggests a role for somatomedin in fetal growth and possibly in the maintenance of pregnancy. Serum somatomedin-C was measured using a highly specific, heterologous radioimmunoassay (RIA) and a less specific membrane binding assay (MBA) which is more sensitive to the influence of somatomedins other than somatomedin-C. The assays were validated for mouse serum by showing that serum concentrations were reduced in genetically growth hormone-deficient mice and in hypophysectomized mice and were increased by growth hormone therapy. As in the human, the RIA measures only a portion of the somatomedin-C present in mouse serum. This “covering up” of somatomedin is attributed to the presence of serum binding proteins and is corrected by treatment of serum samples with acid. By both RIA and MBA, serum somatomedin concentrations are low in fetal and newborn mice, begin to rise in the fourth postnatal week, and reach adult values by 7 weeks of age. The chromatographic pattern of adult mouse serum on Sephacryl 200 is similar to that observed with human sera: The immunoreactive material elutes at apparent molecular weights of 140,000 and 30,000–40,000. The elution profile of125I-labeled somatomedin-C bound to components of serum is nearly identical to the pattern of endogenous activity. As with human serum, somatomedin-C in acidified mouse serum elutes at a lower molecular weight, coincident with insulin and purified somatomedin-C. Maternal serum somatomedin declines in the last half of gestation at the time when placental lactogen levels rise. Along with the absolute decline in somatomedin content is the appearance of unsaturated sites on somatomedin binding proteins. These findings are unexpected and unexplained since somatomedin rises late in pregnancy in humans and several lines of evidence suggest that placental lactogen has the capacity to stimulate somatomedin production. We previously have presented evidence that explants of multiple fetal mouse tissues synthesize somatomedin-C. The present study shows that the immunoreactive somatomedin-C in fetal mouse serum shares identical characteristics with those reported previously for media obtained from mouse liver explants. It seems possible that somatomedin's actions are exerted primarily at or near its site of production and that circulatory levels do not reflect the importance of somatomedin-C on fetal growth. While elucidation of the dramatic developmental changes in serum content and molecular forms of somatomedin-C and in somatomedin binding proteins may be essential to clarifying the role of somatomedin on fetal growth, proof that somatomedin stimulates fetal growth will depend in large part on studies of its biological actions on fetal tissues.