17-beta-Estradiol upregulates COX-2 in the rat oviduct.
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.
Pérez Martínez
S
S
Laboratory of Physiopathology of Pregnancy and Labor, Center for Pharmacological and Botanical Studies (CEFYBO, CONICET-UBA), Paraguay 2155, CP (C1121ABG), Buenos Aires, Argentina. perezms@fmed.uba.ar
Hermoso
M
M
Farina
M
M
Ribeiro
M L
ML
Rapanelli
M
M
Espinosa
M
M
Villalón
M
M
Franchi
A
A
D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D030762:Estrous Cycle / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D000077239:Meloxicam; D008565:Membrane Proteins / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology; D010057:Oviducts / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011959:Receptors, Estradiol / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D052246:Cyclooxygenase 2 Inhibitors; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011453:Prostaglandins; D011959:Receptors, Estradiol; D013449:Sulfonamides; D013843:Thiazines; D013844:Thiazoles; D013629:Tamoxifen; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D011374:Progesterone; D004958:Estradiol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; D000077239:Meloxicam