Kalinyak J E, Hoffman A R, Perlman A J
Medical Service, Department of Veterans Affairs, Palo Alto, CA 94304.
J Endocrinol Invest. 1991 Sep;14(8):647-53. doi: 10.1007/BF03347886.
The renin-angiotensin-system (RAS) is active in fetal and neonatal life. This study was undertaken to examine the ontogenic regulation of angiotensinogen (AT) gene expression and angiotensin II (A II) receptors in liver and brain. AT gene expression was studied in fetal, neonatal, adult and aged rats, using slot blot hybridization to quantify AT mRNA levels. During fetal life (gestational days 15-20), AT mRNA was more abundant in brain than in liver. Soon after birth, brain AT mRNA levels increased to a concentration 3 fold above fetal levels. In contrast, liver AT mRNA abundance increased 30-fold within 12 h of birth. Aging (3-20 months) resulted in a gradual decrease in AT mRNA in both the brain and liver. Liver A II receptors in the neonate were 2-fold higher than in the fetus, but returned to fetal levels by 8 weeks of age. In the brain, A II receptor abundance increased to a level 75% above fetal levels in 7 days old animals, but returned to fetal levels by 14 days of age. These studies suggest than in the fetus, the liver is not the primary source of AT but that unknown factors at parturition result in a dramatic increase in liver AT mRNA. In contrast, the more modest increases in brain AT mRNA parallel the gradual maturation of the CNS. In both tissues, further aging resulted in a gradual decrease in AT mRNA, reflecting either increased sensitivity to feedback downregulation by A II or age related increases in other extrahepatic sites of AT synthesis. Age related changes were also found in the A II receptor in both the liver and brain.
肾素-血管紧张素系统（RAS）在胎儿期和新生儿期是活跃的。本研究旨在探讨肝脏和大脑中血管紧张素原（AT）基因表达及血管紧张素II（A II）受体的个体发生调控。采用狭缝印迹杂交法对胎儿、新生儿、成年和老年大鼠的AT mRNA水平进行定量，研究AT基因表达。在胎儿期（妊娠第15 - 20天），大脑中的AT mRNA比肝脏中更丰富。出生后不久，大脑中AT mRNA水平增加到胎儿水平的3倍。相反，肝脏中AT mRNA丰度在出生后12小时内增加了30倍。衰老（3 - 20个月）导致大脑和肝脏中AT mRNA逐渐减少。新生儿肝脏中的A II受体比胎儿高2倍，但在8周龄时恢复到胎儿水平。在大脑中，7日龄动物的A II受体丰度增加到比胎儿水平高75%，但在14日龄时恢复到胎儿水平。这些研究表明，在胎儿期，肝脏不是AT的主要来源，但分娩时的未知因素导致肝脏中AT mRNA急剧增加。相反，大脑中AT mRNA较适度的增加与中枢神经系统的逐渐成熟平行。在这两种组织中，进一步衰老导致AT mRNA逐渐减少，这反映了对A II反馈下调的敏感性增加或与年龄相关的其他肝外AT合成部位的增加。在肝脏和大脑的A II受体中也发现了与年龄相关的变化。
