Evaluation of the contribution of cyclooxygenase 1 and cyclooxygenase 2 to the production of PGE2 and PGF2 alpha in epithelial cells from bovine endometrium

Abstract

In ruminants, the production of prostaglandins by the endometrium is critical for recognition of pregnancy. In the absence of an embryonic signal, luteolytic pulses of PGF(2 alpha) are released by the uterus. In contrast, the presence of a viable conceptus reduces the production of PGF(2 alpha) relative to PGE(2) and prevents luteolysis through the release of trophoblastic interferon (IFN-tau). Initially, it was thought that epithelial and stromal endometrial cells were specialized in the production of a single type of prostaglandin. However, purified cell populations of both types of cell can produce PGF(2 alpha) and PGE(2); therefore, selective production of PGF(2 alpha) and PGE(2) must be regulated within each type of cell. Two distinct prostaglandin synthases, cyclooxygenase 1 and cyclooxygenase 2, are involved in prostaglandin production and each may catalyse the production of a different prostaglandin. This possibility was investigated in cultured epithelial cells from bovine endometrium. Cells were treated with oxytocin or arachidonic acid, and expression of cyclooxygenase 1 and cyclooxygenase 2 proteins was monitored over time and correlated with prostaglandin accumulation. Cells were also treated with increasing doses of inhibitors of cyclooxygenase 1 or cyclooxygenase 2 (non-steroidal anti-inflammatory drugs; NSAIDs) with or without arachidonic acid or oxytocin: flurbiprofen (0-50 micromol l(-1)) was used as a non-selective inhibitor; valeryl salicylate (0-500 micromol l(-1)) was used as a cyclooxygenase 1 inhibitor and NS-398 (0-1 micromol l(-1)) was used as a cyclooxygenase 2 inhibitor. After stimulation with arachidonic acid or oxytocin, prostaglandin production and expression of cyclooxygenase 2 protein were increased. All inhibitors were able to block basal and stimulated prostaglandin production. These results indicate that in endometrium most, if not all, prostaglandin production is probably processed through cyclooxygenase 2.