Physiological significance of human placental aminopeptidases

我们试图通过胎盘中生物活性肽激素及其降解蛋白酶的相互关系来了解妊娠的病理生理。研究结果表明：(1)从人胎盘cDNA文库中分离到一个编码P-LAP的4084个碱基对的cDNA克隆。推导出的序列在N端附近包含一个疏水区，表明该酶是II型积分膜蛋白。(2)人胎盘中催产素和抗利尿素降解蛋白酶为P-LAP。(3)人胎盘中生长抑素降解蛋白酶为P-LAP。P-LAP可能不仅通过调节生长抑素的浓度，还通过调节胎儿胎盘循环中的血管活性肽（如血管加压素）的浓度参与胎儿的发育。(4)人胎盘血管紧张素II降解的起始蛋白酶为氨基肽酶A和氨基肽酶N （AP-N）。(5)胎盘AP-N （CD13）降解免疫调节肽，如簇状肽、胸腺喷肽和脾喷肽。AP-N可能通过调节免疫调节肽的浓度参与妊娠免疫。临床研究结果表明：(1)随着妊娠的推进，血清中氨基肽酶P增高，而氨基肽酶P可降解缓激肽。(2) P-LAP可用于监测产后妊娠和早产。(3)我们发现正常妊娠时脉冲多普勒S/D比值与P-LAP活性有显著相关性。妊娠血清P-LAP活性可能通过调节胎儿血管抑制素的浓度来反映脐动脉血管阻力。

We tried to understand pathophysiology in pregnancy via interrelationship between bioactive peptide hormones and their degradation proteases in placenta.1. Basic Research We showed the following evidences :(1) We isolated a cDNA clone with 4084 base pairs encoding P-LAP from a human placental cDNA library. The deduced suquence contains a hydrophobic region near the N terminus, suggesting that the enzyme is a type II intergral membrane protein.(2) The oxytocin and vasopressin degradation protease in human placenta is P-LAP.(3) The somatostatin degradation protease in human placenta is P-LAP.P-LAP might be involved in the development of the fetus via regulation not only the concentration of somatostatin but also vasoactive peptides such as vasopressin in the feto-placental circulation.(4) The initiating protease of angiotensin II degradation in human placental in aminopeptidase A and aminopeptidase N (AP-N).(5) Placental AP-N (CD13) degrades immunomodulating peptides such as tuftsin, thymopentin and splenopentin. AP-N might be involved in the immunology of pregnancy via regulating the concentration of immunomodulating peptides.2. Clinical Research We showed the following evidences :(1) Aminopepidase P,which might degrade bradykinin, increases in pregnancy sera with advancing gestation.(2) P-LAP in useful for monitoring post date pregnancy and premature delivery.(3) We found the significant correlation between pulsed Doppler S/D ratio and P-LAP activity in normal pregnancy. The P-LAP activity in pregnancy sera might reflect the vascular resistance in umbilical artery via regulation the concentration of fetal vasopression.