Oxytocin and prostaglandin interactions in pregnancy and at parturition

The demise of the corpus luteum is brought about by an interaction between ovarian oxytocin and uterine prostaglandin F2 alpha (PGF2 alpha) release in sheep. Indirect evidence suggests that a similar, but intra-ovarian, mechanism may also be involved in luteal regression in primates. During early pregnancy, a specific class of interferon (omega interferon) is released from the developing embryo in sheep and this interferon inhibits pulsatile release of uterine PGF2 alpha. Studies in ovariectomized, steroid-treated ewes indicate that conceptus secretory proteins inhibit pulsatile secretion of PGF2 alpha directly via an effect on prostaglandin synthesis and indirectly by maintaining plasma progesterone concentrations that inhibit the development of endometrial oxytocin receptors which normally occurs at the time of luteolysis. As pregnancy progresses, there is an increase in basal secretion of PGF2 alpha and PGE2 from the uterus into the fetal and maternal circulation. The release of maternal PGF2 alpha, but not PGE2, in response to oxytocin is also increased in late pregnancy. Endometrial oxytocin receptor concentrations follow a similar pattern, except at parturition where there appears to be downregulation of receptors. However, the release of PGF2 alpha in response to oxytocin remains high at this time and is further increased if the progesterone receptors are blocked with the anti-progestin RU486. The dissociation between oxytocin receptor numbers and release of prostaglandins in response to oxytocin is also observed under other physiological situations, such as during seasonal anoestrus and after long-term ovariectomy, and requires further investigation. The role of oxytocin in the initiation of labour remains controversial. Although oxytocin concentrations in maternal and fetal plasma are not increased until parturition, uterine oxytocin receptor concentrations, uterine activity and maternal PGF2 alpha release in response to oxytocin are high in late pregnancy. Uterine activity and PG release is not altered by oxytocin in the fetal circulation at any stage of late gestation. We have used the oxytocin analogue CAP to investigate further the possible role of oxytocin in the initiation of labour. CAP can inhibit oxytocin-induced PGF2 alpha release in cyclic sheep, at luteolysis, and in late pregnant sheep by binding to, and blocking, uterine oxytocin receptors. CAP does not inhibit basal fetal or maternal PGF2 alpha or PGE2 concentrations in late pregnancy or at parturition. CAP inhibits oxytocin-induced uterine activity and delays, but does not prevent, the increase in uterine activity associated with labour in this species.(ABSTRACT TRUNCATED AT 400 WORDS)