MECHANISMS REGULATING PROSTAGLANDIN-F2-ALPHA SECRETION FROM THE BOVINE ENDOMETRIUM

The mechanism that regulates luteolytic PGF(2 alpha) secretion as stim ulated by oxytocin is thought to involve induction of the inositol (1, 4,5)-trisphosphate-diacylglycerol second messenger system, which mobil izes intracellular calcium and activates protein kinase C. In Experime nt 1, endometrial explants taken from heifers on d 18.5 to 19.5 postes trus had increased PGF(2 alpha) secretion after treatment with 1 mu M calcium ionophore A23187 to increase intracellular calcium, 100 nM pho rbol 12-myristate 13-acetate to activate protein kinase C, and 100 nM oxytocin. The stimulatory effects of oxytocin and calcium ionophore A2 3187 plus phorbol 12-myristate 13-acetate did not differ from each oth er. In Experiment 2, endometrial explants taken from cows on d 18.5 to 19.5 postestrus had increased PGF(2 alpha) secretion after treatment with 0.2 and 2 mu M thapsigargin to mobilize intracellular calcium tha t was sensitive to inositol (1,4,5)-trisphosphate. Secretion of PGF(2 alpha) was also increased by 100 nM oxytocin and was influenced by the interaction of thapsigargin and oxytocin such that 100 nM oxytocin di d not further increase the secretion of PGF(2 alpha) in the presence o f 2 mu M thapsigargin. In Experiment 3, 100 nM oxytocin stimulated gre ater production of inositol trisphosphate and total inositol phosphate s in the endometrium of cyclic cows than in the endometrium of pregnan t cows on d 16.5 to 17.0 postestrus, although luteolysis was not yet i nitiated in the cyclic cows. These results are consistent with the hyp othesis that the activation of the inositol (1,4,5)-trisphosphate-diac ylglycerol second messenger system by oxytocin is involved in the stim ulation of PGF(2 alpha) secretion from the endometrium during late die strus in cows.