Corticotropin-releasing hormone (CRH) promotes inflammation in human pregnant myometrium: the evidence of CRH initiating parturition?
Abstract
CONTEXT: An increasing body of evidence indicates that human labor, either term or preterm, is an inflammatory event. CRH has been implicated to be a trigger of human parturition. OBJECTIVE: To investigate whether CRH induces the cascades of inflammation in human pregnant myometrium, thereby leading to activation of uterus. DESIGN: The myometrial tissues were obtained from pregnant women who were in labor or not in labor at term. The output of cytokines and prostaglandins (PGs) was determined by Multiplex and ELISA. Western blot analysis was used to determine the levels of uterine activation proteins (UAPs). RESULTS: The levels of chemokines and cytokines as well as activated nuclear factor-κB (NF-κB) were increased in the term labor group more than the not term labor group. CRH stimulated production of a number of chemokines and cytokines in cultured uterine smooth muscle cells (USMCs), which induced chemotaxis of monocytes. These effects were mediated by CRH receptor 1 (CRHR1) and dependent on adenylyl cyclase/protein kinase (PKA) and NF-κB signaling. Cocultures of CRH-treated USMCs with monocytes greatly enhanced the output of cytokines and chemokines as well as PGs in cultures and increased the expression of uterine activation proteins (UAPs) in USMCs. IL-1β, IL-6, and TNF-α stimulated the expression of UAPs and output of PGs in USMCs. CONCLUSIONS: CRH induces the production of chemokines and cytokines in myometrium at term and subsequently results in the cascade of inflammation in uterus. The inflammation induced by CRH can lead to activation of uterus.
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These chemokines and cytokines activate the uterus through induction of an inflammatory response and recruitment of immune cells.
“CRH also stimulated the production of chemokines and cytokines in cultured uterine smooth muscle cells, which have been shown to activate the uterus through the induction of an inflammatory response and the recruitment of immune cells [67,68].”
From Stress and the HPA Axis: Balancing Homeostasis and Fertility. (2017) · cites this paper as [67]
CRH stimulated production of chemokines and cytokines in cultured uterine smooth muscle cells.
“CRH also stimulated the production of chemokines and cytokines in cultured uterine smooth muscle cells, which have been shown to activate the uterus through the induction of an inflammatory response and the recruitment of immune cells [67,68].”
From Stress and the HPA Axis: Balancing Homeostasis and Fertility. (2017) · cites this paper as [67]
CRH promotes labor, partly by altering immune processes that affect uterine muscle contraction and fetal membrane strength.
“This pathway has been of greatest interest in development of spontaneous PTB, as CRH is known to promote labor, including through immunomodulatory effects on myometrial contractility and fetal membrane integrity (e.g., Li and Challis, 2005; You et al., 2014).”
From Childhood stress and birth timing among African American women: cortisol as biological mediator (2017) · cites this paper as You et al., 2014
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Cited by
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Stress and the HPA Axis: Balancing Homeostasis and Fertility.
Joseph, D., & Whirledge, S. (2017) · International journal of molecular sciences · doi:10.3390/ijms18102224 · Cited by 290 · see citing works
“CRH also stimulated the production of chemokines and cytokines in cultured uterine smooth muscle cells, which have been shown to activate the uterus through the induction of an inflammatory response and the recruitment of immune cells [67,68].”
BackgroundChildhood stress and birth timing among African American women: cortisol as biological mediator
Gillespie, S. L., Christian, L. M., Alston, A. D., & Salsberry, P. J. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.06.009 · Cited by 38 · see citing works
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- Authors
- You, X., Liu, J., Xu, C., Liu, W., Zhu, X., Li, Y., Sun, Q., Gu, H., & Ni, X.
- Affiliations
- Second Military Medical University (CN)
- Changhai Hospital (CN)
- Corresponding author
- Ni, Xin
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2014-02-01
- Volume
- 99
- Issue
- 2
- Pages
- E199-E208
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2000850861
- Cited by
- 56
- References
- 47
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 2 · 2015: 8 · 2014: 2
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31101067)
- Changhai Hospital of Shanghai
- Topics
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- corticotropin-releasing factor, myometrium, childbirth, inflammation, term labor, uterine smooth muscle cells, monocytes, chemokines, cytokines, prostaglandins, NF-κB signaling, CRHR1, IL-1β, interleukin-6, TNF-α
- MeSH terms
- Adult, Cells, Cultured, Corticotropin-Releasing Hormone, Female, Humans, Inflammation, Labor, Obstetric, Myometrium, Pregnancy, Cytokines, NF-kappa B, Chemokines, Parturition
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