Endocrine and Paracrine Regulation of Birth at Term and Preterm*
Abstract
We have examined factors concerned with the maintenance of uterine quiescence during pregnancy and the onset of uterine activity at term in an animal model, the sheep, and in primate species. We suggest that in both species the fetus exerts a critical role in the processes leading to birth, and that activation of the fetal hypothalamic-pituitary-adrenal axis is a central mechanism by which the fetal influence on gestation length is exerted. Increased cortisol output from the fetal adrenal gland is a common characteristic across animal species. In primates, there is, in addition, increased output of estrogen precursor from the adrenal in late gestation. The end result, however, in primates and in sheep is similar: an increase in estrogen production from the placenta and intrauterine tissues. We have revised the pathway by which endocrine events associated with parturition in the sheep come about and suggest that fetal cortisol directly affects placental PGHS expression. In human pregnancy we suggest that cortisol increases PGHS expression, activity, and PG output in human fetal membranes in a similar manner. Simultaneously, cortisol contributes to decreases in PG metabolism and to a feed-forward loop involving elevation of CRH production from intrauterine tissues. In human pregnancy, there is no systemic withdrawal of progesterone in late gestation. We have argued that high circulating progesterone concentrations are required to effect regionalization of uterine activity, with…
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Placental CRH is identical to hypothalamic CRH both biologically and in its response to stress.
“The main agent of this axis is Corticotropin Releasing Hormone (CRH); placental CRH is identical to hypothalamic CRH both biologically and in its response to stress [20].”
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].”
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“The main agent of this axis is Corticotropin Releasing Hormone (CRH); placental CRH is identical to hypothalamic CRH both biologically and in its response to stress [20].”
Background
- Authors
- Challis, J. R. G., Matthews, S. G., Gibb, W., & Lye, S. J.
- Affiliations
- Mount Sinai Hospital (CA)
- University of Toronto (CA)
- University of Ottawa (CA)
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2000-10-01
- Volume
- 21
- Issue
- 5
- Pages
- 514-550
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W2129666165
- Cited by
- 995
- References
- 6
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 19 · 2023: 24 · 2022: 29 · 2021: 26 · 2020: 27 · 2019: 26 · 2018: 28 · 2017: 90 · 2016: 30 · 2015: 47 · 2014: 33 · 2013: 62 · 2012: 47
- FWCI
- 7.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- childbirth, preterm labor, uterine quiescence, fetal hypothalamic-pituitary-adrenal axis, fetal cortisol, prostaglandin E2, placental estrogens, fetal membranes, corticotropin-releasing factor, progesterone, sheep model, primate pregnancy
- MeSH terms
- Adrenal Glands, Animals, Female, Fetal Organ Maturity, Homeostasis, Humans, Hydrogen-Ion Concentration, Hypothalamus, Labor, Obstetric, Obstetric Labor, Premature, Myometrium, Pituitary Gland, Pregnancy, Uterine Contraction, Uterus, Paracrine Communication
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