Corticotropin-releasing factor, vasopressin, and prostaglandins mediate, and nitric oxide restrains, the hypothalamic-pituitary-adrenal response to acute local inflammation in the rat.

Turnbull, A V; Rivier, C

doi:10.1210/endo.137.2.8593789

Cited by 95Stress Responses and CortisolAdrenal Hormones and DisordersNeuropeptides and Animal Physiology

Corticotropin-releasing factor, vasopressin, and prostaglandins mediate, and nitric oxide restrains, the hypothalamic-pituitary-adrenal response to acute local inflammation in the rat.

Turnbull, A V, Rivier, C·1996·Endocrinology

DOI 10.1210/endo.137.2.8593789

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Abstract

The present study determined the plasma ACTH and corticosterone responses of the rat to acute local inflammation induced by the im injection of a small volume of turpentine. In response to tissue injury, ACTH and corticosterone concentrations rose rapidly, peaked at 1 h, and returned toward basal values by 3 h after turpentine injection. As acute inflammation developed, plasma interleukin-6 bioactivity increased significantly, and ACTH and corticosterone levels exhibited a secondary rise. These secondary responses were maximum 6-12 h after turpentine administration, persisted for 20-28 h, and were statistically significant regardless of the normal circadian variations in ACTH and corticosterone secretion. Injection of neutralizing anti-CRF antiserum 7 h after turpentine produced a complete reversal, whereas antiarginine vasopressin (anti-AVP) caused a partial (approximately 40%) inhibition, of inflammation-induced ACTH secretion. The cyclooxygenase inhibitor, ibuprofen (10 mg/kg, iv), like CRF antiserum, rapidly and completely reversed turpentine-induced ACTH secretion. In contrast, the nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester (30 mg/kg, iv), produced a significant enhancement of the ACTH response within 30 min of its injection. Measurement of plasma interleukin-6 bioactivity and fever showed that neither anti-CRF, anti-AVP, ibuprofen, nor Nw-nitro-L-arginine methyl ester acutely influenced the local inflammatory process itself, suggesting that these agents interacted directly with the hypothalamo-pituitary-adrenal axis. These data demonstrate that the ACTH response to local inflammation is mediated by synergistic actions of CRF and AVP, and that both stimulatory (PGs) and inhibitory (nitric oxide) intermediates regulate this response.

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The importance of CRF after TPS-induced inflammation is demonstrated by reversal of the ACTH response with anti-CRF serum.
“The importance of CRF, after TPS-induced inflammation, has been demonstrated by reversal of the ACTH response with anti-CRF serum (5).”
From Interleukin-6 is an afferent signal to the hypothalamo-pituitary-adrenal axis during local inflammation in mice (2003) · cites this paper as [5]

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Authors: Turnbull, A. V., & Rivier, C.
Affiliations: Salk Institute for Biological Studies (US)
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 1996-02
Volume: 137
Issue: 2
Pages: 455-463
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/endo.137.2.8593789
OpenAlex: W2060082940
Cited by: 95
References: 49
Citations by year: 2026: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 2
FWCI: 7.63
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: Johns Hopkins University
National Institutes of Health
National Institute of Mental Health (MH-51774, R01MH051774)
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, vasopressin, prostaglandins, nitric oxide, hypothalamic-pituitary-adrenal axis, ACTH secretion, corticosterone, turpentine-induced inflammation, interleukin-6, ibuprofen, cyclooxygenase, fever
MeSH terms: Acute Disease, Adrenocorticotropic Hormone, Animals, Arginine Vasopressin, Circadian Rhythm, Corticotropin-Releasing Hormone, Hypothalamo-Hypophyseal System, Inflammation, Male, Nitric Oxide, Pituitary-Adrenal System, Prostaglandins, Time Factors, Interleukin-6, Rats, Sprague-Dawley, Rats

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Corticotropin-releasing factor, vasopressin, and prostaglandins mediate, and nitric oxide restrains, the hypothalamic-pituitary-adrenal response to acute local inflammation in the rat.

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