title: Agonist-Dependent Downregulation of Progesterone Receptors in Human Cervical Stromal Fibroblasts.
abstract: Progesterone (P(4)) maintains uterine quiescence during the majority of pregnancy, whereas diminished progesterone receptor (PR) expression and/or activity (ie, functional P(4) withdrawal) promotes parturition. To investigate the regulation of PR expression in cervical stroma, fibroblasts from premenopausal hysterectomy specimens were prepared. Greater than 99% of the cultures were vimentin positive (mesenchymal cell marker) with only occasional cytokeratin-8 positivity (epithelial cell marker) and no evidence of CD31-positive (endothelial cell marker) cells. Cells were immunolabeled with antibodies directed against PRs (PR-A and PR-B), estrogen receptor α (ER-α), and glucocorticoid receptor-α/β (GR-α/β). All cells were uniformly immunopositive for ER-α and GR-α/β but did not express PRs. Incubation of cells with 10(-8) mol/L 17β-estradiol induced a time-dependent increase in PR-A and PR-B messenger RNAs (mRNAs) by quantitative real-time polymerase chain reactions and proteins by immunoblotting and immunofluorescence. Incubation of cervical fibroblasts with PR ligands (medroxyprogesterone acetate or Org-2058) downregulated PR-A and PR-B levels. Coincubation of cells with PR ligands plus RU-486, a PR antagonist, partially abrogated agonist-induced receptor downregulation. Dexamethasone, a pure glucocorticoid, had no inhibitory effect on PR expression. These results indicate that progestins and estrogens regulate PR expression in cervical fibroblasts. We postulate that hormonal regulation of PR expression in the cervical stroma may contribute to functional P(4) withdrawal in preparation for parturition.
authors.affiliation: Division of Maternal-Fetal Medicine and Laboratory of Perinatal Research, Department of Obstetrics and Gynecology, The Ohio State University, College of Medicine and Wexner Medical Center, Columbus, OH, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Ackerman
authors.affiliation: Division of Maternal-Fetal Medicine and Laboratory of Perinatal Research, Department of Obstetrics and Gynecology, The Ohio State University, College of Medicine and Wexner Medical Center, Columbus, OH, USA.
authors.forename: Taryn L
authors.initials: TL
authors.lastname: Summerfield
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Mesiano
authors.affiliation: Division of Maternal-Fetal Medicine and Laboratory of Perinatal Research, Department of Obstetrics and Gynecology, The Ohio State University, College of Medicine and Wexner Medical Center, Columbus, OH, USA Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Schatz
authors.affiliation: Division of Maternal-Fetal Medicine and Laboratory of Perinatal Research, Department of Obstetrics and Gynecology, The Ohio State University, College of Medicine and Wexner Medical Center, Columbus, OH, USA Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lockwood
authors.affiliation: Division of Maternal-Fetal Medicine and Laboratory of Perinatal Research, Department of Obstetrics and Gynecology, The Ohio State University, College of Medicine and Wexner Medical Center, Columbus, OH, USA Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH, USA kniss.1@osu.edu.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Kniss
mesh_terms: D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D011282:Pregnenediones / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D006727:Hormone Antagonists; D011282:Pregnenediones; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; C020175:16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione; D015735:Mifepristone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate
keywords: cervix; estradiol; parturition; progesterone receptor; receptor downregulation