Dexamethasone and Indomethacin Inhibition of Structural Luteolysis in Rats: An Intraluteal Mechanism Involving Prolonged Activation of Phospholipase A2 Activity and Prostaglandin Synthesis May Facilitate the Luteolytic Process.

Abstract

We previously showed that luteal cytosolic phospholipase A2 and prostaglandin F2α level which rises during functional luteolysis persisted during the following structural luteolysis in rats. To investigate the possible role of the sustained activation of luteal prostaglandin synthesis in the accomplishment of luteolysis, we studied the influence of systematic injection with a phospholipase A2 inhibitor, dexamethasone, and a cyclooxygenase inhibitor, indomethacin, on structural luteolysis. Repeated administration of the inhibitors to mothers for seven days postpartum partially reversed suckling stimuli-induced decline in pregnant corpus luteum weight. The inhibitors also inhibited exogenous prolactin-induced structural regression in immature pseudopregnant rats, and the inhibition of luteal cytosolic phospholipase A2 activity and prostaglandin F2α level was confirmed in this experimental model. Immunohistochemical study revealed that dexamethasone-treated corpus luteum had a significantly lower number of infiltrating macrophages. Moreover, fibroblastic proliferation in that corpus luteum seemed to be attenuated by both dexamethasone and indomethacin. Considered together with our previous findings, the data suggest that the persistent activation of luteal phospholipase A2 activity and prostaglandin generation may function to facilitate the luteolytic process and that this mechanism mediates prolactin-induced structural luteolysis in rats.