ACTIVITY OF PHOSPHOLIPASE-C AND RELEASE OF PROSTAGLANDIN-F2-ALPHA BY ENDOMETRIAL TISSUE FROM EWES DURING THE ESTROUS-CYCLE AND EARLY-PREGNANCY

Oxytocin appears to play an important role in regulating uterine secre tion of prostaglandin F2alpha (PGF2alpha) in sheep. Changes in uterine secretion of PGF2alpha throughout the oestrous cycle and early pregna ncy may be due to changes in the intracellular regulatory pathways tha t control synthesis of PGF2alpha in response to oxytocin. In this expe riment, caruncular endometrial tissue was collected from ewes througho ut the oestrous cycle and early pregnancy. Endometrial tissue was incu bated in vitro to assess release of PGF2alpha and activity of phosphol ipase C (PLC) in response to oxytocin. Release of PGF2alpha in the pre sence of arachidonic acid was used to assess the activity of prostagla ndin H-2 endoperoxide synthase (PGS). In non-pregnant ewes, oxytocin s timulated release of PGF2alpha from endometrial tissue collected on da ys 14 and 16, but not on days 4-7, 10 or 12 after oestrus. This coinci ded with times when oxytocin stimulated the activity of PLC. Release o f PGF2alpha was enhanced by the addition of arachidonic acid to tissue s collected on days 12, 14 and 16 after oestrus. As with tissue from n onpregnant ewes, oxytocin could stimulate release of PGF2alpha on days 14 and 16 of early pregnancy. Yet, oxytocin had no effect on activity of PLC in tissue from pregnant ewes. Release of PGF2alpha in the pres ence of arachidonic acid by tissue from pregnant ewes was similar to t hat in nonpregnant ewes at comparable times after oestrus. On the basi s of these results, it was concluded that (1) an increase in the abili ty of oxytocin to stimulate activity of PLC occurs coincidentally with the increase in its ability to stimulate release of PGF2alpha from ov ine endometrial tissue; (2) activity of PGS in endometrial tissue incr eases at least 2 days before an increase in secretory responsiveness t o oxytocin; (3) the ability of the conceptus to inhibit release of PGF 2alpha in response to oxytocin in vivo, as demonstrated in several pre vious reports, is lost during in vitro incubation in the absence of th e conceptus; and (4) oxytocin stimulates release of PGF2alpha by endom etrial tissue from pregnant ewes despite the fact that oxytocin does n ot stimulate activity of PLC in this same tissue. Thus, the role of PL C in mediating the stimulatory effect of oxytocin on endometrial secre tion of PGF2alpha appears questionable.