Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.

Muglia, L J; Jacobson, L; Weninger, S C; Luedke, C E; Bae, D S; Jeong, K H; Majzoub, J A

doi:10.1172/jci119487

Cited by 115Stress Responses and CortisolAdrenal Hormones and DisordersCircadian rhythm and melatonin

Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.

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Muglia, L J, Jacobson, L, Weninger, S C, Luedke, C E, Bae, D S, Jeong, K H, Majzoub, J A·1997·Journal of Clinical Investigation

DOI 10.1172/jci119487PMC PMC508144

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Abstract

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 demonstrate a sexual dichotomy in response to stress, indicating a mechanism independent of CRH.
“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]
The Discussion (p. 2923) reports that female CRH-knockout mice can produce glucocorticoids during acute restraint stress, supporting a stress response despite CRH deficiency. The paper compares male and female knockout mice for circadian corticosterone levels, but does not establish a male–female difference in their responses to stress. (LLM, conf=0.84)
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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
ORCID: Muglia, L J
Jacobson, L
Weninger, S C
Bae, D S
Majzoub, J A
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1997-06-15
Volume: 99
Issue: 12
Pages: 2923-2929
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci119487
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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Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.

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