Spatola E, Pescovitz O H, Marsh K, Johnson N B, Berry S A, Gelato M C
Department of Medicine, State University of New York, Stony Brook 11794.
Endocrinology. 1991 Sep;129(3):1193-200. doi: 10.1210/endo-129-3-1193.
The placenta is a chimeric organ that produces all the components of the hypothalamic-pituitary GH axis. We propose that placental GH-releasing hormone (GHRH) stimulates placental GH-like hormones which in turn stimulate production of the insulin-like growth factors (IGFs), IGF-I and IGF-II, and these placental IGFs are important for growth and development of the placenta as well as the fetus. To test this hypothesis, pregnant rats were given either GHRH antisera or preimmune sera ip from days 7-19 of gestation. Fetuses were killed on day 19, and IGF-I and IGF-II tissue and serum concentrations in the mother and fetus were measured by RIA. IGF-II receptor content was measured by Western analysis. IGF-I and IGF-II messenger (m) RNA levels were measured in the placentas as well as in the fetal livers. The GHRH antibody titer was highest at day 19 of gestation but continued to be present through day 20 of postnatal development. Although placental weights did not differ, antibody-treated animals had higher placental IGF-I and IGF-II levels (I, 108 +/- 6 (SD); II, 126 +/- 5 ng/g, respectively) vs. control animals (I, 88 +/- 2.5 (SD); II, 48 +/- 11 ng/g) in pooled specimens. The IGF-II receptor was also up-regulated in placentas from antibody-treated mothers. The fetuses of antibody-treated (A) mothers were larger than the controls (C) (A, 2.615 g; C, 2.49 g, P less than 0.05). Levels of both IGFs were significantly increased in livers of antibody treated fetuses (IGF-I: A, 15 +/- 1 (SD); C, 12 +/- 0.8 ng/g; and IGF-II: A, 295 +/- 10 (SD); C, 233 +/- 10 (SD) ng/g). In addition, the concentration of the IGF-II receptor in liver of antibody-treated fetuses was also increased. Further, pooled fetal sera from antibody-treated fetuses had higher levels of IGF-II than controls (A, 950 ng/ml; C, 700 ng/ml), and the circulating IGF-II receptor was increased as measured by Western analysis. In the liver, IGF-II mRNA levels of antibody-treated fetuses were increased to 117% of controls, whereas IGF-I mRNA levels were undetectable. The placenta showed no increase in placental lactogen or GH mRNA, whereas IGF-II and GHRH mRNA were slightly increased in antibody-treated animals. In conclusion, these data suggest that GHRH may interact with the IGFs in a different fashion during prenatal development then during postnatal development.(ABSTRACT TRUNCATED AT 400 WORDS)
胎盘是一个嵌合器官，可产生下丘脑 - 垂体生长激素（GH）轴的所有组成部分。我们提出，胎盘生长激素释放激素（GHRH）刺激胎盘类生长激素，而后者又刺激胰岛素样生长因子（IGF）即IGF - I和IGF - II的产生，并且这些胎盘IGF对胎盘以及胎儿的生长发育很重要。为了验证这一假设，在妊娠第7至19天给怀孕大鼠腹腔注射GHRH抗血清或免疫前血清。在第19天处死胎儿，并通过放射免疫分析（RIA）测量母鼠和胎儿体内IGF - I和IGF - II的组织及血清浓度。通过蛋白质印迹分析测量IGF - II受体含量。在胎盘以及胎儿肝脏中测量IGF - I和IGF - II信使（m）RNA水平。GHRH抗体滴度在妊娠第19天最高，但在出生后发育的第20天仍存在。尽管胎盘重量没有差异，但合并标本中，抗体处理组动物的胎盘IGF - I和IGF - II水平较高（分别为I，108±6（标准差）；II，126±5 ng/g），而对照组动物为（I，88±2.5（标准差）；II，48±11 ng/g）。抗体处理组母鼠胎盘的IGF - II受体也上调。抗体处理组（A）母鼠的胎儿比对照组（C）大（A，2.615 g；C，2.49 g；P<0.05）。抗体处理组胎儿肝脏中两种IGF的水平均显著升高（IGF - I：A，15±1（标准差）；C，12±0.8 ng/g；IGF - II：A，295±10（标准差）；C，233±10（标准差）ng/g）。此外，抗体处理组胎儿肝脏中IGF - II受体的浓度也增加。此外，抗体处理组胎儿的合并血清中IGF - II水平高于对照组（A，950 ng/ml；C，700 ng/ml），通过蛋白质印迹分析测量，循环中的IGF - II受体增加。在肝脏中，抗体处理组胎儿的IGF - II mRNA水平增加至对照组的117%，而IGF - I mRNA水平未检测到。胎盘催乳素或GH mRNA在胎盘中没有增加，而在抗体处理组动物中IGF - II和GHRH mRNA略有增加。总之，这些数据表明，GHRH在产前发育过程中与IGF的相互作用方式可能与产后发育过程不同。（摘要截断于400字）
