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 fractions and pregnancy sera was studied in the presence of selective inhibitors and the antibody against pregnancy serum oxytocinase (placental leucine aminopeptidase; EC3.4.11.3) by measuring the released amino acids by high-performance liquid chromatography. We also studied the degradation of other brain-gut hormones, such as glucagon, growth hormone, growth hormone releasing factor, and insulin, in the human placenta and found that the human placenta degrades somatostatin, glucagon, and growth 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 releasing 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 somatostatin levels in the umbilical artery are about 2.5-fold higher than those in the umbilical vein. Our data on somatostatin levels in umbilical artery and vein of intrauterine growth retardation human fetuses showed that the ratio umbilical artery/vein is around 1. Since insulin is known to be the primary hormone regulating the ratio of fetal growth, our data suggest that the degradation of somatostatin in the placenta is decreased and that elongation of somatostatin effects may result in the inhibition of insulin secretion in the intrauterine growth retardation fetus.
Mizutani
S
S
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
Goto
K
K
Tsujimoto
M
M
Nakazato
H
H
Matsuzawa
K
K
Furuhashi
Y
Y
Arii
K
K
Tomoda
Y
Y
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004064:Digestive System / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism; D006728:Hormones / Q000378:metabolism*; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007931:Leucyl Aminopeptidase / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D008969:Molecular Sequence Data; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D013004:Somatostatin / Q000378:metabolism*; D013379:Substrate Specificity
D000596:Amino Acids; D006728:Hormones; D007328:Insulin; D019382:Human Growth Hormone; D013004:Somatostatin; D005934:Glucagon; D013007:Growth Hormone-Releasing Hormone; D007931:Leucyl Aminopeptidase