Mechanisms regulating prostaglandin F2 alpha secretion from the bovine endometrium

The mechanism that regulates luteolytic PGF2 alpha secretion as stimulated by oxytocin is thought to involve induction of the inositol (1,4,5)-trisphosphate-diacylglycerol second messenger system, which mobilizes intracellular calcium and activates protein kinase C. In Experiment 1, endometrial explants taken from heifers on d 18.5 to 19.5 postestrus had increased PGF2 alpha secretion after treatment with 1 microM calcium ionophore A23187 to increase intracellular calcium, 100 nM phorbol 12-myristate 13-acetate to activate protein kinase C, and 100 nM oxytocin. The stimulatory effects of oxytocin and calcium ionophore A23187 plus phorbol 12-myristate 13-acetate did not differ from each other. In Experiment 2, endometrial explants taken from cows on d 18.5 to 19.5 postestrus had increased PGF2 alpha secretion after treatment with 0.2 and 2 microM thapsigargin to mobilize intracellular calcium that was sensitive to inositol (1,4,5)-trisphosphate. Secretion of PGF2 alpha was also increased by 100 nM oxytocin and was influenced by the interaction of thapsigargin and oxytocin such that 100 nM oxytocin did not further increase the secretion of PGF2 alpha in the presence of 2 microM thapsigargin. In Experiment 3, 100 nM oxytocin stimulated greater production of inositol trisphosphate and total inositol phosphates in the endometrium of cyclic cows than in the endometrium of pregnant cows on d 16.5 to 17.0 postestrus, although luteolysis was not yet initiated in the cyclic cows. These results are consistent with the hypothesis that the activation of the inositol (1,4,5)-trisphosphate-diacylglycerol second messenger system by oxytocin is involved in the stimulation of PGF2 alpha secretion from the endometrium during late diestrus in cows.