title: Progesterone inhibits transcriptional activation of human chorionic gonadotropin-alpha gene through protein kinase A pathway in trophoblast cells.
abstract: The purpose of this study was to analyze the mechanism of transcriptional inhibition of human chorionic gonadotropin-alpha (hCGalpha) gene by progesterone in trophoblast cells. We stably transfected -290 bp hCGalpha promoter-CAT constructs (-290halphaCAT) into Rcho-1 cells and monitored the promoter activities. Differentiation-dependent activation of -290 bp hCGalpha promoter containing a tandem repeat of cAMP response element (CRE) was inhibited by progesterone in a dose-dependent manner. To further analyze the mechanism of the progesterone action, Rcho-1 cells stably transfected with -290halphaCAT were treated with forskolin in the presence of progesterone. Progesterone inhibited forskolin-induced transcriptional activation of hCGalpha gene. Moreover, progesterone inhibited forskolin-induced transcriptional activation of CRE-CRE-tk-CAT. These results suggest that progesterone may inhibit cAMP-induced transcriptional activation of hCGalpha gene through CRE. Although progesterone did not alter the amount of CRE-binding protein (CREB), which is a main transcriptional factor bound to CRE(s) on hCGalpha promoter, progesterone abolished forskolin-induced CREB phosphorylation. In addition, pretreatment with progesterone abolished forskolin-induced activation of nuclear protein kinase A (PKA). In conclusion, progesterone inhibits hCGalpha gene transcription, at least in part, via the CRE region by inhibiting CREB phosphorylation through PKA pathway in trophoblast cells.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University, Faculty of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. yamamoto@gyne.med.osaka-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: H
authors.initials: H
authors.lastname: Kurachi
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Nishio
authors.forename: M
authors.initials: M
authors.lastname: Sakata
authors.forename: K
authors.initials: K
authors.lastname: Tasaka
authors.forename: Y
authors.initials: Y
authors.lastname: Murata
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D021122:Protein Subunits; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects*; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D015292:Glycoprotein Hormones, alpha Subunit; D021122:Protein Subunits; D005576:Colforsin; D011374:Progesterone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases