Enhanced Up‐Regulation of Corticotropin‐Releasing Hormone Gene Expression in Response to Restraint Stress in the Hypothalamic Paraventricular Nucleus of Oxytocin Gene‐Deficient Male Mice
Abstract
The neuropeptide oxytocin is released not only into the blood, but also within the brain in response to various stressors. Accumulating evidence suggests that central oxytocin may play a major role in the regulation of neuroendocrine responses to stress. In the present study, using the oxytocin knockout mouse model, we tested whether oxytocin might act to attenuate stress-induced up-regulation of corticotropin-releasing hormone (CRH) mRNA expression in the brain. The expression of CRH mRNA in the paraventricular nucleus (PVN) after 4 h of restraint stress was examined in oxytocin gene-deficient (OTKO), wild-type and heterozygous male mice using in situ hybridization histochemistry. We found that basal levels of CRH mRNA were not different among the three genotypes. Although restraint stress resulted in a significant increase of CRH mRNA expression in the PVN regardless of genotype, the degree of stress induced-up-regulation was significantly higher in OTKO mice than in wild-type mice. The effects of restraint stress on the expression of the arginine vasopressin (AVP) and the oxytocin genes were also examined. Unlike CRH mRNA, basal expression (in nonstressed control groups) of AVP mRNA in OTKO mice, as well as oxytocin mRNA in heterozygous mice, was significantly lower in the PVN and the supraoptic nucleus than in wild-type mice. After restraint stress, the expression of AVP mRNA was significantly increased in the PVN of OTKO mice compared to the nonstressed control group, wh…
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OT may regulate HPA axis gain at the PVN level as well as the pituitary.
“suggesting that OT may regulate HPA axis gain at the PVN level as well as the pituitary.”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Nomura et al., 2003
Global deletion of OT in female mice results in increased stress-induced CORT secretion and Crh mRNA expression in the PVN.
“Furthermore, global deletion of OT in female mice results in increased stress-induced CORT secretion and Crh mRNA expression in the PVN (Mantella, Vollmer, Rinaman, Li, & Amico, 2004; Nomura et al., 2003)”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Nomura et al., 2003
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“Furthermore, global deletion of OT in female mice results in increased stress-induced CORT secretion and Crh mRNA expression in the PVN (Mantella, Vollmer, Rinaman, Li, & Amico, 2004; Nomura et al., 2003), suggesting that OT may regulate HPA axis gain at the PVN level as well as the pituitary.”
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- Authors
- Nomura, M., Saito, J., Ueta, Y., Muglia, L. J., Pfaff, D. W., & Ogawa, S.
- Affiliations
- Rockefeller University (US)
- University of Occupational and Environmental Health Japan (JP)
- Washington University in St. Louis (US)
- Corresponding author
- Ogawa, S.
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2003-10-21
- Volume
- 15
- Issue
- 11
- Pages
- 1054-1061
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- OpenAlex
- W2125589549
- Cited by
- 69
- References
- 3
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 2 · 2013: 5 · 2012: 1
- FWCI
- 8.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (62147)
- Japan Society for the Promotion of Science
- National Institute of Mental Health
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, corticotropin-releasing factor, restraint stress, hypothalamic paraventricular nucleus, vasopressin, supraoptic nucleus, Fos expression, stress response, neuroendocrine regulation, amygdala, bed nucleus of the stria terminalis, lateral septum, medial preoptic area
- MeSH terms
- Animals, Arginine Vasopressin, Corticotropin-Releasing Hormone, Immunohistochemistry, Male, Oxytocin, Paraventricular Hypothalamic Nucleus, Restraint, Physical, RNA, Messenger, Stress, Physiological, Supraoptic Nucleus, Up-Regulation, Oncogene Proteins v-fos, In Situ Hybridization, Mice, Knockout, Mice
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