On the function of placental corticotropin‐releasing hormone: a role in maternal‐fetal conflicts over blood glucose concentrations
Abstract
Throughout the second and third trimesters, the human placenta (and the placenta in other anthropoid primates) produces substantial quantities of corticotropin-releasing hormone (placental CRH), most of which is secreted into the maternal bloodstream. During pregnancy, CRH concentrations rise over 1000-fold. The advantages that led selection to favour placental CRH production and secretion are not yet fully understood. Placental CRH stimulates the production of maternal adrenocorticotropin hormone (ACTH) and cortisol, leading to substantial increases in maternal serum cortisol levels during the third trimester. These effects are puzzling in light of widespread theory that cortisol has harmful effects on the fetus. The maternal hypothalamic-pituitary-adrenal (HPA) axis becomes less sensitive to cortisol during pregnancy, purportedly to protect the fetus from cortisol exposure. Researchers, then, have often looked for beneficial effects of placental CRH that involve receptors outside the HPA system, such as the uterine myometrium (e.g. the placental clock hypothesis). An alternative view is proposed here: the beneficial effect of placental CRH to the fetus lies in the fact that it does stimulate the production of cortisol, which, in turn, leads to greater concentrations of glucose in the maternal bloodstream available for fetal consumption. In this view, maternal HPA insensitivity to placental CRH likely reflects counter-adaptation, as the optimal rate of cortisol production for the fetus exceeds that for the mother. Evidence pertaining to this proposal is reviewed.
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Throughout second and third trimesters of pregnancy, human placental syncytiotrophoblasts secrete substantial quantities of CRH, with peak levels at parturition.
“Throughout the second and third trimesters of pregnancy, human placental syncytiotrophoblasts secrete substantial quantities of CRH, with peak levels occurring at parturition [59].”
From Stress and the HPA Axis: Balancing Homeostasis and Fertility. (2017) · cites this paper as [59]
Cites
The Developmental Origins of Adult Disease
Barker, D. J. P. (2004) · Journal of the American College of Nutrition · doi:10.1080/07315724.2004.10719428 · Cited by 1,854 · see citing works
Genetic conflicts in human pregnancy
Haig, D. (1993) · The Quarterly Review of Biology · doi:10.1086/418300 · Cited by 1,253 · see citing works
Seckl, J. R., & Holmes, M. C. (2007) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0515 · Cited by 754 · see citing works
Weinstock, M. (2005) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2004.09.006 · Cited by 706 · see citing works
Wadhwa, P. D., Garite, T. J., Porto, M., Glynn, L., Chicz-DeMet, A., Dunkel-Schetter, C., & Sandman, C. A. (2004) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2004.06.070 · Cited by 402 · see citing works
Ishimoto, H., & Jaffe, R. B. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0001 · Cited by 379 · see citing works
Maternal Psychological Distress, Prenatal Cortisol, and Fetal Weight
Diego, M. A., Jones, N. A., Field, T., Hernandez-Reif, M., Schanberg, S., Kuhn, C., & Gonzalez-Garcia, A. (2006) · Psychosomatic Medicine · doi:10.1097/01.psy.0000238212.21598.7b · Cited by 302 · see citing works
Brunton, P. J., Russell, J. A., & Douglas, A. J. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01735.x · Cited by 298 · see citing works
Glynn, L. M., Schetter, C. D., Chicz-DeMet, A., Hobel, C. J., & Sandman, C. A. (2007) · Peptides · doi:10.1016/j.peptides.2007.04.005 · Cited by 99 · see citing works
Stress and placental resistance measured by doppler ultrasound in early and mid-pregnancy
Harville, E. W., Savitz, D. A., Dole, N., Herring, A. H., Thorp, J. M., & Light, K. C. (2008) · Ultrasound in Obstetrics & Gynecology · doi:10.1002/uog.5344 · Cited by 41 · see citing works
Plasma corticotropin-releasing factor concentrations in the baboon during pregnancy
Goland, R. S. (1992) · Endocrinology · doi:10.1210/en.131.4.1782 · Cited by 35 · see citing works
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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
“Throughout the second and third trimesters of pregnancy, human placental syncytiotrophoblasts secrete substantial quantities of CRH, with peak levels occurring at parturition [59].”
BackgroundCuffe, J. S. M., Walton, S. L., Singh, R. R., Spiers, J. G., Bielefeldt‐Ohmann, H., Wilkinson, L., Little, M. H., & Moritz, K. M. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.272856 · Cited by 128 · see citing works
Craddock, T. J. A., Fritsch, P., Rice, M. A., del Rosario, R. M., Miller, D. B., Fletcher, M. A., Klimas, N. G., & Broderick, G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084839 · Cited by 75 · see citing works
- Authors
- Gangestad, S. W., Caldwell Hooper, A. E., & Eaton, M. A.
- Affiliations
- University of New Mexico (US)
- Corresponding author
- Gangestad, Steven W.
- ORCID
- Gangestad, Steven W.
- Venue
- Biological Reviews
- Publisher
- Wiley
- Published
- 2012-05-08
- Volume
- 87
- Issue
- 4
- Pages
- 856-873
- ISSN
- 0006-3231 (ISSN-L)
- 1464-7931
- 1469-185X
- OpenAlex
- W2093757488
- Cited by
- 54
- References
- 11
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 3 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 1 · 2015: 7 · 2014: 7 · 2013: 1
- FWCI
- 0.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological reviews/Biological reviews of the Cambridge Philosophical Society (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- maternal-fetal conflict, blood glucose, maternal cortisol, ACTH, hypothalamic-pituitary-adrenal axis, myometrium, counter-adaptation, primate placenta, pregnancy
- MeSH terms
- Adaptation, Physiological, Blood Glucose, Corticotropin-Releasing Hormone, Female, Humans, Maternal-Fetal Exchange, Placenta, Pregnancy
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