Cited by 271Estrogen and related hormone effectsPreterm Birth and ChorioamnionitisMaternal and Perinatal Health Interventions

A decline in the levels of progesterone receptor coactivators in the pregnant uterus at term may antagonize progesterone receptor function and contribute to the initiation of parturition

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Condon, Jennifer C., Jeyasuria, Pancharatnam, Faust, Julie M., Wilson, James W., Mendelson, Carole R.·2003·Proceedings of the National Academy of Sciences

Abstract

The molecular events that lead to the onset of labor in humans and in other mammalian species remain unclear. We propose that a decline in coactivators containing histone acetylase activity in myometrium may contribute to the onset of labor by impairing the function of the progesterone–progesterone receptor (PR) complex. As assessed by semiquantitative and real-time RT-PCR, immunohistochemistry, and immunoblotting, expression of the PR coactivators cAMP-response element-binding protein (CREB)-binding protein and steroid receptor coactivators 2 and 3 was decreased in fundal uterine tissue of women in labor. Using the mouse as an animal model, we also found decreased coactivator levels in uterine tissues at term. In both human and mouse, the levels of acetylated histone H3 were also decreased in uterine tissues at term. Administration of trichostatin A, a specific and potent histone deacetylase inhibitor, to pregnant mice late in gestation increased histone acetylation and delayed the initiation of parturition by 24–48 h, suggesting the functional importance of the decline in histone acetylation in the initiation of labor. These findings suggest that the decline in PR coactivator expression and in histone acetylation in the uterus near term may impair PR function by causing a functional progesterone withdrawal. The resulting decrease in expression of PR-responsive genes should increase sensitivity of the uterus to contractile stimuli.

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Crossref · 10.1073/pnas.1633616100

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Authors
Condon, J. C., Jeyasuria, P., Faust, J. M., Wilson, J. W., & Mendelson, C. R.
Affiliations
The University of Texas Southwestern Medical Center (US)
Corresponding author
Mendelson, Carole R.
Venue
Proceedings of the National Academy of Sciences
Published
2003-07-28
Volume
100
Issue
16
Pages
9518-9523
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1992634340
Cited by
270
References
42
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 16 · 2018: 8 · 2017: 11 · 2016: 18 · 2015: 11 · 2014: 12 · 2013: 21 · 2012: 20
FWCI
8.28
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD011149, 3-P01-HD11149-25S1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
  • Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
Keywords
progesterone receptor, transcriptional coactivator, childbirth, labor onset, histone acetylation, histone deacetylase, CREB-binding protein, SRC-2, SRC-3, myometrium, progesterone withdrawal, trichostatin A, acetylated histone H3, term pregnancy, uterus
MeSH terms
Acetyltransferases, Animals, Cell Nucleus, Enzyme Inhibitors, Female, Histones, Humans, Hydroxamic Acids, Immunohistochemistry, Labor, Obstetric, Myometrium, Nuclear Proteins, Pregnancy, Progesterone, Receptors, Progesterone, RNA, Messenger, Transcription Factors, Uterus, Immunoblotting, Oncogene Proteins, Trans-Activators, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, CREB-Binding Protein, Mice, Histone Acetyltransferases, Nuclear Receptor Coactivator 2, Histone Deacetylase Inhibitors, Nuclear Receptor Coactivator 3

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