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Prenatal CRH: An integrating signal of fetal distress

Published online by Cambridge University Press:  02 August 2018

Curt A. Sandman
Curt A. Sandman*
Affiliation:
University of California, Irvine
*
Address correspondence and reprint requests to: Curt A. Sandman, Department of Psychiatry and Human Behavior, University of California, Irvine, One University Drive, Orange, CA 92866; E-mail: [email protected].
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Abstract

Corticotropin-releasing hormone (CRH) is distributed throughout the brain and in peripheral sites but primarily is localized in the paraventricular nucleus of the hypothalamus. It is a “master” stress hormone that is responsible for the synthesis of proopiomelanocortin (POMC) in the anterior pituitary gland. Behaviorally active peptide hormones, including adrenocorticotropin hormone (ACTH) and B-endorphin, are liberated from POMC by enzymes to activate critical processes during stress. CRH is not detectable in the circulation even during extreme stress. However, during human pregnancy, the human placenta expresses the gene for CRH (pCRH) resulting in detectable levels in maternal plasma that increases 20- to 40-fold over the course of gestation. Placental CRH is identical to CRH of hypothalamic origin in size, structure, immunoreactivity, and bioactivity. However, unlike the negative feedback between adrenal cortisol and hypothalamic CRH, cortisol stimulates the synthesis and release of pCRH. The bidirectional release of pCRH into maternal and fetal compartments is associated with regulating the timing of delivery, remodeling the fetal nervous system, and influencing developmental trajectories. Fetal exposure to pCRH during early and late gestation is associated with unique patterns of cortical thinning in school-age children. Placental CRH is elevated in response to physical and behavioral stress and may be an integrative marker of early adversity.

Type
Special Issue Articles
Information
Development and Psychopathology , Volume 30 , Special Issue 3: Developmental Origins of Psychopathology: Mechanisms, Processes, and Pathways Linking the Prenatal Environment to Postnatal Outcomes , August 2018 , pp. 941 - 952
Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

The research reported here was supported by National Institute of Health Grants NS-41298, HD-51852, HD-28413, HD-40967, HD-50662, and HD-65823, and Conte Center award MH-96889. The invaluable contributions to the research described here by my long-time collaborators, Laura Glynn and Elysia Davis, is gratefully acknowledged. The tireless work of many postdocs and research assistants, especially Claudia Buss, Mariann Howland, Cheryl Crippen, Carol Holliday, Quetzal Class, Christina Canino Brown, Megan Faulkner, Kendra Leak, Amanda Appel, and Kevin Head, made these studies possible. I am forever grateful for the mentoring and friendship of Abba Kastin, who introduced me to the wide world of neuropeptides and the research environment of a laboratory chasing a major discovery. Finally, it is impossible to overestimate the critical contributions by the families who participated in the research program, often making as many as 15, 2- to 3-hr visits to the laboratory and sacrificing weekends and holidays to allow us to learn about the most critical period of human life.

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