CONTROL OF BOVINE UTERINE PROSTAGLANDIN-F2-ALPHA RELEASE INVITRO

Prostaglandin F(2α) (PGF(2α)) release from the uterus causes luteolysis in ruminants, and oxytocin is thought to be a regulator of this release. In the present study, we have examined the mechanisms involved in oxytocin stimulation of PGF(2α) secretion of bovine endometrium in vitro. Endometrial tissue explants, obtained from heifers at Day 19 or 20 (n = 3) and Day 0 (estrus, n = 5) of the estrous cycle, were incubated for 2h and 6 h, and PGF(2α) concentration in the medium was determined by radioimmunoassay (RIA). Basal PGF(2α) release increased for up to 6 h and was significantly stimulated after 2 h of incubation with 100 μU and 1000 μU of oxytocin at Day 0 but not at Day 19 or 20. Secretion of PGF(2α) was not affected by cholera toxin (10 ng/ml) or the cyclic nucleotide analogs dibutyryl cyclic adenosine 3',5'-monophosphate and dibutyryl cyclic guanosine 3',5'-monophosphate at a concentration of 1 mM. A protein kinase A inhibitor (500 μM) had no effect on the oxytocin-induced release of PGF(2α). Both the phorbol ester, 12-myristate-13-acetate (100 nM), and the non-phorbol stimulator of protein kinase C, 1-octanoyl-2-acetylglycerol (500 μM), significantly stimulated PGF(2α) secretion to the same extent as oxytocin. Neither basal nor stimulated PGF(2α) release was affected by the calcium ionophore A23187 (0.1 - 5.0 μM). However, PGF(2α) secretion was sensitive to cycloheximide (1 μg/ml) suggesting that protein synthesis may be involved. In conclusion, these data suggest that the stimulation of PGF(2α) by oxytocin is via the protein kinase C effector pathway.