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

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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

DOI 10.1073/pnas.1633616100PMC PMC170950

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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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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.
ORCID: Jeyasuria, Pancharatnam
Mendelson, Carole R.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2003-07-28
Volume: 100
Issue: 16
Pages: 9518-9523
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1633616100
PMC: PMC170950
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: bronze
doi.org
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 › Endocrinology › Estrogen and related hormone effects
Health Sciences › Medicine › Obstetrics and Gynecology › 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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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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