title: Up-regulation of cyclooxygenase-2 gene expression by chorionic gonadotropin during the differentiation of human endometrial stromal cells into decidua.
abstract: Human endometrial stromal cells contain human CG (hCG)/LH receptors and in vitro, hCG/LH can promote stromal cells differentiation into decidua. In the present study, we tested the hypothesis that the treatment of stromal cells with exogenous hCG/LH to promote in up-regulation of cyclooxygenase-2 (COX-2) gene expression. The stromal cells from proliferative phase endometria were cultured for 10 days with 10 ng/ml estradiol and 100 ng/ml progesterone in the presence or absence of increasing concentrations of highly purified hCG. Northern blotting demonstrated that the cells contained a 4.4-kb COX-2 messenger RNA transcript whose levels significantly increased after treatment with hCG. Western blotting showed that the cells contained a 72-kDa COX-2 protein which also significantly increased after treatment with hCG. The effect of hCG on COX-2 messenger RNA and protein was seen at 10 ng/ml and higher concentrations sustained the increased levels. Although human LH mimicked hCG, human FSH, TSH, and isolated alpha- and beta-subunits of hCG had no effect on COX-2 protein levels suggesting that the hCG effect is hormone specific and requires the conformation of native hormone. The effect of hCG on COX-2 protein paralleled the increase in media prostaglandin E2 levels indicating that the increased COX-2 gene and half-life of its transcripts to determine the molecular mechanism of hCG action. The results showed that hCG treatment had no significant effect on transcription rate of the COX-2 gene. On the other hand, treatment with hCG significantly increased the half-life of the COX-2 transcripts from 2.6 h in the control to 6.7 h after treatment. In summary, we conclude that treatment of human endometrial stromal cells with exogenous hCG to promote their differentiation into decidua results in an up-regulation of COX-2 gene expression by increasing the stability of the transcripts.
authors.affiliation: Department of Obstetrics and Gynecology, University of Louisville School of Medicine, Kentucky 40292, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Han
authors.forename: Z M
authors.initials: ZM
authors.lastname: Lei
authors.forename: C V
authors.initials: CV
authors.lastname: Rao
mesh_terms: D000328:Adult; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D003656:Decidua / Q000166:cytology*; D015232:Dinoprostone / Q000378:metabolism; D004717:Endometrium / Q000166:cytology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008565:Membrane Proteins; D008875:Middle Aged; D011374:Progesterone / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology; D015854:Up-Regulation
chemical_list: D006063:Chorionic Gonadotropin; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone