Evidence that Corticotropin-Releasing Hormone Modulates Myometrial Contractility during Human Pregnancy
Abstract
As human pregnancy advances, CRH increases exponentially and is hypothesized to trigger the transition from myometrial quiescence to active contractions at labor. Paradoxically, CRH stimulates cAMP production, suggesting it should cause relaxation. To evaluate CRH as a mediator of quiescence, the effect of CRH on contractions in preterm and term myometria with concurrent progesterone (P4) was determined. In late gestation, we hypothesized that high concentrations of CRH down-regulate agonist-activated-cAMP relaxatory pathways and that increased phosphodiesterase (PDE) activity induces heterologous down-regulation of agonist-activated-cAMP pathways. CRH caused dose-dependent relaxation of spontaneously contracting myometrial strips of 31 ± 8% (mean ± sem; n = 12) and 35 ± 20% (n = 3) in term and preterm samples, respectively. CRH with P4 pretreatment caused a 40 ± 13% (n = 4) reduction in contractility, whereas in matched samples, CRH alone exerted a 26 ± 6% (n = 4) reduction, with a shift of CRH dose-response curves (P < 0.01, ANOVA). Pretreatment of strips with 10−7m CRH did not attenuate relaxation induced by subsequent CRH (n = 3) or salbutamol (β2-agonist) treatment (n = 9). PDE inhibition by rolipram showed a 2.2- and 1.5-fold increase in maximal relaxation induced by CRH and salbutamol, respectively, with a shift of both dose-response curves (P < 0.05 and P < 0.01, ANOVA). In conclusion, CRH at physiological concentrations acts synergistically with P4 contributing to myometrial quiescence. P4 withdrawal may reduce CRH-mediated relaxation. Our functional model does not support homologous or heterologous down-regulation of agonist-stimulated-cAMP pathways by high CRH concentrations. PDE inhibition potentiates CRH and salbutamol-induced relaxation. Up-regulation of PDEs, through chronic cAMP elevation by CRH, could provide a mechanism for down-regulation of agonist-stimulated-cAMP pathways at term.
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Increases of CRH early in pregnancy have predicted the onset of preterm labor.
“Increases of CRH early in pregnancy have predicted the onset of preterm labor in ours and other’s results [20–25].”
From The mastery lifestyle intervention to reduce biopsychosocial risks for pregnant Latinas and African Americans and their infants: protocol for a randomized controlled trial (2022) · cites this paper as [21]
The introduction (p. 5617) says maternal CRH levels rise from the second trimester and increase sharply shortly before delivery. The Discussion and results examine CRH’s effects on myometrial contractions, but do not report whether early-pregnancy CRH increases predict preterm labor (searched for early-gestation CRH and prediction of preterm delivery). (LLM, conf=0.72)
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- Authors
- Tyson, E. K., Smith, R., & Read, M.
- Affiliations
- John Hunter Hospital (AU)
- Corresponding author
- Tyson, Elisa K.
- ORCID
- Smith, Roger
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2009-10-21
- Volume
- 150
- Issue
- 12
- Pages
- 5617-5625
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1969781989
- Cited by
- 47
- References
- 47
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 1 · 2013: 2 · 2012: 7
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
- Keywords
- corticotropin-releasing factor, uterine contractility, myometrial quiescence, progesterone, phosphodiesterase, cAMP signaling, rolipram, salbutamol, preterm labor, labor onset, beta2-adrenergic agonists
- MeSH terms
- Adult, Albuterol, Corticotropin-Releasing Hormone, Dose-Response Relationship, Drug, Drug Synergism, Female, Gestational Age, Humans, Maternal Age, Muscle Relaxation, Myometrium, Phosphodiesterase Inhibitors, Pregnancy, Progesterone, Uterine Contraction, Tocolytic Agents, Rolipram, Young Adult, In Vitro Techniques
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