Oxytocin modulates the onset of murine parturition by competing ovarian and uterine effects.
Recent analysis of mice deficient in both oxytocin (OT) and cyclooxygenase-1 has shown that OT exerts significant effects on both the ovarian corpus luteum and the uterine myometrium during pregnancy. To better define the roles of OT during pregnancy, we evaluated OT action and OT receptor regulation in wild-type and OT-deficient knockout (KO) mice. Continuous infusion of OT revealed that OT can either delay labor at low doses or initiate preterm labor at high doses. The infusion rates of OT necessary for these effects were reduced in OT KO mice. The dose of OT that delayed labor also delayed the normal decrease in plasma progesterone late in gestation, implicating a primary effect on the corpus luteum. Consistent with this hypothesis, luteal OT receptor expression exceeded that of the myometrium until luteolysis occurred. We propose that the downregulation of OT receptors in the corpus luteum and induction of OT receptors in the myometrium serve to shift the predominant consequence of OT action during murine pregnancy from labor inhibition to labor promotion.
Imamura
T
T
Departments of Pediatrics, Molecular Biology and Pharmacology, and Obstetrics and Gynecology, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Missouri 63110, USA.
Luedke
C E
CE
Vogt
S K
SK
Muglia
L J
LJ
D000818:Animals; D015152:Blotting, Northern; D003338:Corpus Luteum / Q000737:chemistry / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D007743:Labor, Obstetric / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009215:Myometrium / Q000737:chemistry / Q000502:physiology*; D010121:Oxytocin / Q000235:genetics* / Q000494:pharmacology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D010121:Oxytocin