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 l uteum and the uterine myometrium during pregnancy. To better define the rol es of OT during pregnancy, we evaluated OT action and OT receptor regulatio n 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, lute al 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 p redominant consequence of OT action during murine pregnancy from labor inhi bition to labor promotion.