Oxytocin hypersensitivity in pregnant P-LAP deficient mice.
OBJECTIVE
Oxytocin (OT) is the strongest uterotonic substance and has been used widely to induce labor. The physiological importance of OT in modulating the initiation and progression of labor remains unclear. In this study, we showed the roles of OT with onset of labor and also the arginine vasopressin (AVP) effect on urine volume in vivo using both wild type (WT) and placental leucine aminopeptidase (P-LAP)-deficient (KO) mice.


METHODS
OT (1, 2, 2.5 U/day) or recombinant P-LAP (0.01 U/day) was continuously infused from gestation day 15.5 in WT and P-LAP KO mice. Duration until onset of labor was observed. Before and after administration of AVP (1 U/day) in WT and P-LAP KO mice, urine volume was measured.


RESULTS
A significant shortening of pregnancy term was observed in P-LAP KO mice. Continuous infusion of OT (1 U/day) revealed that P-LAP KO mice resulted in premature delivery (OT hypersensitivity). We could observe a significant decrease of urine volume in P-LAP KO mice by administration of AVP. Administration of recombinant P-LAP in WT mice resulted in the delay of the onset of labor about 1.5 days compared with control mice.


CONCLUSIONS
Our present study shows that the regulation of the onset of labor mainly depends on OT and its degradation by P-LAP and also the possible role of P-LAP in the regulation of urine output. P-LAP might be involved in the increased OT sensitivity just prior to onset of labor and also in the onset of labor by degradation of OT.
Ishii
Masakazu
M
Department of Medical Science of Proteases, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan. masai@med.nagoya-u.ac.jp
Naruse
Katsuhiko
K
Hattori
Akira
A
Tsujimoto
Masafumi
M
Ishiura
Shoichi
S
Numaguchi
Yasushi
Y
Murohara
Toyoaki
T
Kobayashi
Hiroshi
H
Mizutani
Shigehiko
S
D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000378:metabolism; D010122:Cystinyl Aminopeptidase / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D007743:Labor, Obstetric; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010053:Ovary / Q000502:physiology; D010121:Oxytocin / Q000008:administration & dosage / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000502:physiology
D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D010121:Oxytocin; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase