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

ABSTRACT

We investigated the regulation of cyclooxygenase-2 (COX-2) by 17-beta-estradiol (E2) 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 microg/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 E2 was partially reverted by tamoxifen (1 mg/rat), an E2 receptor antagonist. Estradiol treatment also increased prostaglandins (PGs) synthesis: 6-keto-PGF(1alpha) (40%), a stable metabolite of prostacyclin (PGI2), PGF(2alpha) (40%) and PGE2 (50%). Tamoxifen completely suppressed this enhancement. In order to discriminate which isoform of COX was implicated in the stimulatory effect of E2 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 E2. All together, these data indicate that E2 could upregulate COX-2 expression and activity in the rat oviduct and that the stimulatory effect of E2 may be receptor-mediated.