Impaired Basal and Restraint-Induced Epinephrine Secretion in Corticotropin-Releasing Hormone- Deficient Mice1
Abstract
CRH is thought to play a role in responses of the adrenocortical and adrenomedullary systems during stress. To investigate the role of CRH in stress-induced secretions of corticosterone and epinephrine, we subjected wild-type (WT) and CRH-deficient (knockout, KO) mice to restraint, and analyzed plasma corticosterone, plasma catecholamines, and adrenal phenylethanolamine N-methyltransferase (PNMT) gene expression and activity before and during 3 h of restraint. Plasma corticosterone increased over 40-fold in WT mice, but minimally in CRH KO mice. Adrenal corticosterone content tended to increase in CRH KO mice, although to levels 5-fold lower than that in WT mice. CRH KO mice had significantly lower plasma epinephrine and higher norepinephrine than WT mice at baseline, and delayed epinephrine secretion during restraint. Adrenal PNMT messenger RNA content in CRH KO mice tended to be lower than that in WT mice, though the degree of induction was similar in both genotypes. PNMT enzyme activity was significantly lower in CRH KO mice. Pharmacological adrenalectomy abolished restraint-induced corticosterone secretion and PNMT gene expression in WT mice, consistent with an absolute requirement of glucocorticoids for PNMT gene expression. We conclude that glucocorticoid insufficiency in CRH KO mice leads to decreased basal and restraint-induced plasma epinephrine and adrenal PNMT gene expression and enzyme activity.
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Plasma epinephrine reaches its peak from 30 to 90 min after onset of immobilization stress.
“The plasma level of epinephrine reaches its peak from 30 min to 90 min after the onset of immobilization stress (Jeong et al., 2000; Kvetnansky et al., 2006; Qing et al., 2020).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Jeong et al., 2000
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- Authors
- Jeong, K.-H., Jacobson, L., Pacák, K., Widmaier, E. P., Goldstein, D. S., & Majzoub, J. A.
- Affiliations
- Harvard University (US)
- National Institutes of Health (US)
- Boston University (US)
- Corresponding author
- Majzoub, Joseph A.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2000-03
- Volume
- 141
- Issue
- 3
- Pages
- 1142-1150
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1974684692
- Cited by
- 87
- References
- 57
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 7 · 2015: 3 · 2013: 7 · 2012: 1
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29dk049333-03, 5r01dk050511-06)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK49333, R01 DK50511)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- corticotropin-releasing factor, epinephrine secretion, norepinephrine, corticosterone, restraint stress, phenylethanolamine N-methyltransferase, glucocorticoid insufficiency, adrenalectomy, stress response, catecholamines
- MeSH terms
- Adrenalectomy, Animals, Corticosterone, Corticotropin-Releasing Hormone, Epinephrine, Glucocorticoids, Male, Mice, Inbred C57BL, Restraint, Physical, RNA, Messenger, Stress, Psychological, Tyrosine 3-Monooxygenase, In Situ Hybridization, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Mice
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