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Agonist-Dependent Downregulation of Progesterone Receptors in Human Cervical Stromal Fibroblasts

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Abstract

Progesterone (P4) maintains uterine quiescence during the majority of pregnancy, whereas diminished progesterone receptor (PR) expression and/or activity (ie, functional P4 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 P4 withdrawal in preparation for parturition.

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Authors and Affiliations

  1. 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, 395 West 12th Avenue, 43210, Columbus, OH, USA

    William E. Ackerman IV MD, Taryn L. Summerfield MS, Frederick Schatz PhD, Charles J. Lockwood MD, MHCM & Douglas A. Kniss PhD

  2. Department of Obstetrics, Gynecology and Reproductive Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH, USA

    Sam Mesiano PhD

  3. Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    Frederick Schatz PhD & Charles J. Lockwood MD, MHCM

  4. Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH, USA

    Douglas A. Kniss PhD

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  1. William E. Ackerman IV MD
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  2. Taryn L. Summerfield MS
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  3. Sam Mesiano PhD
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  4. Frederick Schatz PhD
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  5. Charles J. Lockwood MD, MHCM
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  6. Douglas A. Kniss PhD
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Correspondence to Douglas A. Kniss PhD.

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Ackerman, W.E., Summerfield, T.L., Mesiano, S. et al. Agonist-Dependent Downregulation of Progesterone Receptors in Human Cervical Stromal Fibroblasts. Reprod. Sci. 23, 112–123 (2016). https://doi.org/10.1177/1933719115597787

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