Effect of an oxytocin receptor antagonist on ovarian and uterine synthesis and release of prostaglandin F2 alpha in pseudopregnant rats.

There is substantial experimental evidence suggesting that oxytocin has a role in luteolysis in ruminates. Endogenous pulses of uterine prostaglandin (PG) F2 alpha occur synchronously with pulses of oxytocin during luteolysis; leading us to propose a possible feedback loop between uterine PGF2 alpha and luteal oxytocin. In rates, the mechanism whereby oxytocin acts has not been well elucidated. In the present report, the effects of an oxytocin receptor antagonist in pseudopregnant rats were investigated. Pseudopregnancy was induced in immature female rats by gonadotrophin treatment; this resulted in the formation of corpus luteum that remained functional for 9 +/- 1 days. The pseudopregnant rats were assigned to one of the following four groups. In the first group the relationship between the release of ovarian and uterine PGF2 alpha was tested. We also studied the serum progesterone during the pseudopregnancy. We found that PGF2 alpha released into the incubation medium from ovaries of pseudopregnant rats increased (p < 0.05) and was maximal on day 9 of pseudopregnancy. This concentration remained high until day 10 of pseudopregnancy and then decreased. The PGF2 alpha released from the uterus to the incubation medium rose (p < 0.05) on day 8 of pseudopregnancy and reached the peak value on day 10. the serum progesterone was increased (p < 0.001) on day 2 pseudopregnancy and was greater on day 5 (p < 0.001). The second and third group received a specific oxytocin receptor antagonist (1-deamino-2-O-methyltyrosine) in two different concentrations (0.05 or 0.2 mumol/l before the peak of PG release. Both doses employed decreased (p < 0.001) the release into the incubating medium of PGF2 alpha from ovaries and uterus. Indeed, after the treatment, the progesterone levels were higher (p < 0.001) than control on day 10 of pseudopregnancy. In the fourth group, a potent inhibitor of cyclooxygenase activity was administered on day 8 of pseudopregnancy into the ovarian bursa. The serum progesterone levels increased (p < 0.01) compared to control suggesting a possible role of ovarian PG in the luteolytic phase of the corpus luteum regression. Thus, our findings show that oxytocin is luteolytic in pseudopregnant rats and this action is mediated by oxytocin receptors, as it was blocked by a specific oxytocin receptor antagonist.