Physiological significance of human placental aminopeptidases

我们试图通过生物活性多肽激素与其在胎盘中的降解酶之间的相互关系来了解妊娠的病理生理学。基础研究：(1)从人胎盘c DNA文库中克隆了编码P-LAP的全长4084个碱基对的c DNA克隆。(2)人胎盘中的催产素和加压素降解酶为P-LAP。(3)人胎盘中的生长抑素降解酶为P-LAP。P-LAP可能不仅通过调节胎儿胎盘循环中生长抑素的浓度，而且还通过调节血管活性多肽，如血管加压素，参与胎儿-胎盘循环的发育。(4)人胎盘中血管紧张素II降解的起始酶-氨基转移酶A和氨基转移酶N(AP-N)。(5)胎盘氨基转移酶A和氨基转移酶N(AP-N)降解免疫调节肽。胸腺五肽和脾五肽。结论：1.AP-N可能通过调节免疫调节肽的浓度参与妊娠免疫。临床研究发现：(1)孕期血清中可降解缓激肽的氨基磷脂酶P随着孕周的延长而升高，(2)P-LAP对过期妊娠和早产的监测有一定价值。(3)正常妊娠组的脉冲多普勒S/D比值与P-LAP活性呈显著正相关。妊娠血清中P-LAP活性可能通过调节胎儿血管加压素浓度来反映脐动脉的血管阻力。

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.