Possible involvement of placental peptidases that degrade gonadotropin-releasing hormone (GnRH) in the dynamic pattern of placental hCG secretion via GnRH degradation.
The presence of an extrahypothalamic gonadotropin releasing hormone (GnRH) in human placenta is well known and this decapeptide is presumed to play an important role in the regulation of the function and growth of human placenta. Immunohistochemistry showed that neutral endopeptidase 24.11 (NEP), a candidate of the responsible enzyme of GnRH degradation, is highly expressed on the cell surface of trophoblasts. Hydrolysis of GnRH by human villi was studied by measuring liberated amino acids using high performance liquid chromatography. The GnRH degrading activity was 1.53 times higher after incubation with the membrane fraction of first trimester villi than that after incubation with the membrane fraction of term villi. Phosphoramidon, a potent inhibitor of NEP, reduced the liberated amino acids to about a half, suggesting that NEP is a responsible enzyme for GnRH degradation. Ubenimex, which can inhibit several aminopeptidases, also reduced the liberated amino acids to about 50 per cent. O-phenanthroline, EDTA, and thiorphan could inhibit GnRH degradation but inhibitors of post proline endopeptidase could not. Furthermore, GnRH degrading activity of the membrane fraction was reduced remarkably after the membrane fraction was immunotitrated by anti NEP and anti placental leucine aminopeptidase (P-LAP) IgG. In conclusion, NEP and P-LAP are responsible enzymes for GnRH degradation in human villi.
Kikkawa
F
F
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan.
Kajiyama
H
H
Ino
K
K
Watanabe
Y
Y
Ito
M
M
Nomura
S
S
Itakura
A
A
Tsujimoto
M
M
Mizutani
S
S
D000328:Adult; D019138:Antibodies, Blocking / Q000494:pharmacology; D002824:Chorionic Villi / Q000187:drug effects / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000201:enzymology; D007743:Labor, Obstetric; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007931:Leucyl Aminopeptidase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009924:Organ Culture Techniques; D010618:Phenanthrolines / Q000494:pharmacology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011480:Protease Inhibitors / Q000494:pharmacology; D015244:Thiorphan / Q000494:pharmacology
D019138:Antibodies, Blocking; D006020:Glycopeptides; D010618:Phenanthrolines; D011480:Protease Inhibitors; D007987:Gonadotropin-Releasing Hormone; D004492:Edetic Acid; D015244:Thiorphan; D007931:Leucyl Aminopeptidase; D015260:Neprilysin; D007930:Leucine; C012211:ubenimex; C008890:phosphoramidon; C025205:1,10-phenanthroline