Oxytocin appears to play an important role in regulating uterine secretion of prostaglandin F2α (PGF2α) in sheep. Changes in uterine secretion of PGF2α throughout the oestrous cycle and early pregnancy may be due to changes in the intracellular regulatory pathways that control synthesis of PGF2α in response to oxytocin. In this experiment, caruncular endometrial tissue was collected from ewes throughout the oestrous cycle and early pregnancy. Endometrial tissue was incubated in vitro to assess release of PGF2α and activity of phospholipase C (PLC) in response to oxytocin. Release of PGF2α in the presence of arachidonic acid was used to assess the activity of prostaglandin H2 endoperoxide synthase (PGS). In nonpregnant ewes, oxytocin stimulated release of PGF2α from endometrial tissue collected on days 14 and 16, but not on days 4–7, 10 or 12 after oestrus. This coincided with times when oxytocin stimulated the activity of PLC. Release of PGF2α was enhanced by the addition of arachidonic acid to tissues collected on days 12, 14 and 16 after oestrus. As with tissue from nonpregnant ewes, oxytocin could stimulate release of PGF2α on days 14 and 16 of early pregnancy. Yet, oxytocin had no effect on activity of PLC in tissue from pregnant ewes. Release of PGF2α in the presence of arachidonic acid by tissue from pregnant ewes was similar to that in nonpregnant ewes at comparable times after oestrus. On the basis of these results, it was concluded that (1) an increase in the ability of oxytocin to stimulate activity of PLC occurs coincidentally with the increase in its ability to stimulate release of PGF2α from ovine endometrial tissue; (2) activity of PGS in endometrial tissue increases at least 2 days before an increase in secretory responsiveness to oxytocin; (3) the ability of the conceptus to inhibit release of PGF2α in response to oxytocin in vivo, as demonstrated in several previous reports, is lost during in vitro incubation in the absence of the conceptus; and (4) oxytocin stimulates release of PGF2α by endometrial tissue from pregnant ewes despite the fact that oxytocin does not stimulate activity of PLC in this same tissue. Thus, the role of PLC in mediating the stimulatory effect of oxytocin on endometrial secretion of PGF2α appears questionable.
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