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Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.
Open accessAbstract
The normal pattern of daily glucocorticoid production in mammals requires circadian modulation of hypothalamicpituitary-adrenal axis activity. To assess both the factors responsible for imparting this diurnal profile and its physiologic importance, we have exploited corticotropin-releasing hormone (CRH)-deficient mice generated by homologous recombination in embryonic stem cells. CRH-deficient mice have lost normal circadian variations in plasma ACTH and glucocorticoid while maintaining normal circadian locomotor activity. Constant peripheral infusion of CRH produced marked diurnal excursions of plasma glucocorticoid, indicating that CRH acts in part as a permissive factor for other circadian modulators of adrenocortical activity. The presence of atrophic adrenals in CRH-deficient mice without an overt deficit in basal plasma ACTH concentration suggests that the diurnal increase in ACTH is essential to maintain normal adrenal function.
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“CRH KO mice also demonstrate this sexual dichotomy in response to stress, indicating a mechanism independent of CRH (12, 38).”
From Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation (2000) · cites this paper as [38]
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Metadata
- Authors
- Muglia, L. J., Jacobson, L., Weninger, S. C., Luedke, C. E., Bae, D. S., Jeong, K. H., & Majzoub, J. A.
- Affiliations
- Boston Children's Hospital (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Majzoub, J A
- Venue
- Journal of Clinical Investigation
- Published
- 1997-06-15
- Volume
- 99
- Issue
- 12
- Pages
- 2923-2929
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508144
- OpenAlex
- W1992866860
- Cited by
- 115
- References
- 47
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 6 · 2015: 5 · 2014: 6 · 2013: 2 · 2012: 1
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (1p30hd033688-01)
- Pfizer Pharmaceuticals
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 33688)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- corticotropin-releasing factor, circadian rhythm, hypothalamic-pituitary-adrenal axis, ACTH, adrenal atrophy, adrenocortical function, glucocorticoid synthesis
- MeSH terms
- Adrenal Cortex, Adrenocorticotropic Hormone, Animals, Blood Glucose, Circadian Rhythm, Corticosterone, Corticotropin-Releasing Hormone, Female, Glucocorticoids, Insulin, Light, Male, Mice, Inbred C57BL, Motor Activity, Photoperiod, Mice, Knockout, Mice
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