title: Regulation of COX-2 gene expression in rat uterus in vivo and in vitro.
abstract: Prostaglandins are involved in mediating several important processes in mammalian reproduction, including the initiation of parturition. In the present study, we examined the expression in the rat uterus of two-rate limiting enzymes involved in prostaglandin production, cyclooxygenase (COX) 1 and 2. Expression of the COX-2 gene in the pregnant rat uterus gave rise to a single mRNA transcript of approximately 4.4 kb. COX-2 mRNA levels increased 3.5 fold between day 7 of pregnancy and the onset of parturition on day 22. In contrast, COX-1 mRNA levels remained constant during the same period. To investigate factors involved in mediating the regulation of COX-1 and COX-2 gene expression, rat endometrial stromal and epithelial cell lines, were used. In the stroma-derived cell line, CUS-V2, COX-2 gene expression was demonstrated by reverse transcriptase/polymerase chain reaction (RT-PCR) and by immunocytochemistry. In these cells, COX-2 gene expression was inducible by the cytokines interleukin-1 beta and tumor necrosis factor alpha, but not by interleukin-6. The two former cytokines also induced prostaglandin F2 alpha production. In contrast, COX-1 gene expression was constitutive in this cell line. In the endometrial epithelium-derived cell line, CUE-P both COX-1 and COX-2 genes were expressed in a constitutive fashion. In conclusion, the present in vivo and in vitro data indicate that decidual COX-2, but not COX-1, gene expression is regulated during pregnancy and implicate specific cytokines as possible inducers within the decidua.
authors.affiliation: Department of Medicine, Royal Victoria Hospital, Montreal, Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Arslan
authors.forename: H H
authors.initials: HH
authors.lastname: Zingg
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015237:Dinoprost / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D008565:Membrane Proteins; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D014599:Uterus / Q000166:cytology / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat