title: Estrogen negatively regulates rat gonadotropin releasing hormone (rGnRH) promoter activity in transfected placental cells.
abstract: To dissect the functional architecture of the rat gonadotropin releasing hormone (GnRH) gene promoter and its regulation by estrogen, gene transfer studies were performed in a placental cell line. 5'-Deletional constructs demonstrated that cis-acting elements important for rGnRH promoter activity in placenta were contained within a region of the proximal promoter between -73 and -16 bp upstream of the transcription initiation site. In addition, an inhibitory region was found from -903 to -424. Deletion of sequences to -424 which removed the inhibitory region, produced a promoter fragment which exhibited a 50% inhibition of GnRH promoter activity in the presence of estrogen (E) and cotransfected estrogen receptor. Negative regulation by E was retained in constructs deleted to -73 bp. We conclude that sequences important for placental cell expression and estrogen regulation of rGnRH lie within the region from -73 to -16. In addition, potential repressor sequences active in placental cells are present between -903 to 424.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver.
authors.forename: M E
authors.initials: ME
authors.lastname: Wierman
authors.forename: J K
authors.initials: JK
authors.lastname: Kepa
authors.forename: W
authors.initials: W
authors.lastname: Sun
authors.forename: D F
authors.initials: DF
authors.lastname: Gordon
authors.forename: W M
authors.initials: WM
authors.lastname: Wood
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002822:Choriocarcinoma / Q000473:pathology; D003864:Depression, Chemical; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014594:Uterine Neoplasms / Q000473:pathology
chemical_list: D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D007987:Gonadotropin-Releasing Hormone