POSSIBLE EFFECTS OF PLACENTAL LEUCINE AMINOPEPTIDASE ON THE REGULATION OF BRAIN-GUT HORMONES IN THE FETOPLACENTAL UNIT

The hydrolysis of somatostatin by human placental subcellular fraction s and pregnancy sera was studied in the presence of selective inhibito rs and the antibody against pregnancy serum oxytocinase (placental leu cine aminopeptidase; EC3.4.11.3) by measuring the released amino acids by high-performance liquid chromatography. We also studied the degrad ation of other brain-gut hormones, such as glucagon, growth hormone, g rowth hormone releasing factor, and insulin, in the human placenta and found that the human placenta degrades somatostatin, glucagon, and gr owth hormone releasing factor, but not insulin and growth hormone. The degradation velocity of somatostatin was ten times greater than that of growth hormone releasing factor in placental microsomal fractions. Our data suggest that the stimulatory control by growth hormone releas ing factor is dominant in the fetal growth hormone secretion. Our data also identified the somatostatin-degrading protease in human placenta using placental leucine aminopeptidase. It is known that the mean som atostatin levels in the umbilical artery are about 2.5-fold higher tha n those in the umbilical vein. Our data on somatostatin levels in umbi lical artery and vein of intrauterine growth retardation human fetuses showed that the ratio umbilical artery/vein is around 1. Since insuli n is known to be the primary hormone regulating the ratio of fetal gro wth, our data suggest that the degradation of somatostatin in the plac enta is decreased and that elongation of somatostatin effects may resu lt in the inhibition of insulin secretion in the intrauterine growth r etardation fetus.