17-beta-Estradiol upregulates COX-2 in the rat oviduct

Abstract

We investigated the regulation of cyclooxygenase-2 (COX-2) by 17-beta-estradiol (E-2) in the rat oviduct. We observed that COX-2 is expressed mainly in proestrous and estrous stages, periods under estrogenic influence. While exogenous administration of E2 (1 mu g/rat) significantly increased COX-2 protein levels, progesterone did not modify it. COX-2 was mainly localized on oviductal. epithelial cells from estrogenized rat. Induction of COX-2 expression by E-2 was partially reverted by tamoxifen (1 mg/rat), an E-2 receptor antagonist. Estradiol treatment also increased prostaglandins (PGs) synthesis: 6-keto-PGF(1 alpha) (40%), a stable metabolite of prostacyclin (PGI(2)), PGF(2 alpha) (40%) and PGE(2) (50%). Tamoxifen completely suppressed this enhancement. In order to discriminate which isoform of COX was implicated in the stimulatory effect of E-2 on PGs synthesis, oviducts were preincubated with meloxicam (Melo: 10(-9) M) or NS-398 (10(-7) M), two selective COX-2 inhibitors. Both Melo and NS-398 abolished the increase of PGs synthesis stimulated by E-2. All together, these data indicate that E-2 could upregulate COX-2 expression and activity in the rat oviduct and that the stimulatory effect of E-2 may be receptor-mediated