Arginine vasopressin potentiates adrenocorticotropin release induced by ovine corticotropin-releasing factor

DeBold, C R; Sheldon, W R; DeCherney, G S; Jackson, R V; Alexander, A N; Vale, W; Rivier, J; Orth, D N

doi:10.1172/jci111240

Cited by 189Stress Responses and CortisolAdrenal Hormones and DisordersNeuropeptides and Animal Physiology

Arginine vasopressin potentiates adrenocorticotropin release induced by ovine corticotropin-releasing factor

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DeBold, C R, Sheldon, W R, DeCherney, G S, Jackson, R V, Alexander, A N, Vale, W, Rivier, J, Orth, D N·1984·Journal of Clinical Investigation

DOI 10.1172/jci111240PMC PMC425045

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Abstract

Arginine vasopressin (AVP) stimulates ACTH release in man and acts synergistically with synthetic ovine corticotropin-releasing factor (oCRF) in vitro. This study was designed to examine in man the combined effects of synthetic AVP (10 U intramuscularly) and oCRF (1 micrograms/kg intravenously) on ACTH release. Five normal male volunteers participated in five separate experiments: (a) AVP alone; (b) oCRF alone; (c) AVP followed by oCRF 15 min later; (d) simultaneous AVP and oCRF; and (e) insulin-induced hypoglycemia. Plasma immunoreactive ACTH (IR-ACTH) and IR-cortisol were measured for 4 h after injection of each hormone; basal levels for all subjects were less than or equal to 9 +/- 1.2 pg/ml and 4.9 +/- 0.4 micrograms/dl (mean +/- SE), respectively. AVP and oCRF, when given individually, caused rapid rises in IR-ACTH to similar peak levels of 25 +/- 6.6 and 33 +/- 4.6 pg/ml, respectively. AVP given 15 min before oCRF caused a 2.6-fold potentiation of the oCRF response, with a peak IR-ACTH of 85 +/- 4.6 pg/ml. AVP given at the same time as oCRF produced a fourfold potentiation of the peak IR-ACTH response to 132 +/- 11 pg/ml. These ACTH responses were far greater than those previously observed after 30-fold greater doses of oCRF alone. By way of comparison, insulin-induced hypoglycemia caused a peak IR-ACTH of 169 +/- 20 pg/ml. IR-ACTH returned to base line at 60-90 min after AVP alone, whereas the prolonged effect of oCRF was apparent whether it was given alone or in combination with AVP. The mean peak IR-cortisol responses to AVP, oCRF, and AVP given 15 min before oCRF were similar (16.5 +/- 0.9, 16.4 +/- 2.3, and 18.5 +/- 0.8 micrograms/dl, respectively), but the peak IR-cortisol responses to AVP and oCRF given simultaneously and to insulin-induced hypoglycemia were 1.5 and 1.7 times greater, respectively. IR-cortisol returned to base line within 2-3 h after AVP alone, but remained elevated for at least 4 h after oCRF alone or in combination with AVP. These results indicate that AVP acts synergistically with oCRF to release ACTH in man and suggest that AVP may play a physiologic role in modulating the ACTH response mediated by corticotropin-releasing factor.

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On receipt of the neuronal signal from the amygdala and locus coeruleus, numerous neuropeptides are released from the hypothalamus, including arginine vasopressin (AVP) and stress-induced corticotropin-releasing factor/hormone (CRF/H).
“On receipt of the neuronal signal from the amygdala and locus coeruleus, numerous neuropeptides are released from the hypothalamus, including arginine vasopressin (AVP) and stress-induced corticotropin-releasing factor/hormone (CRF/H) (90).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [90]
The Introduction (page unavailable) identifies AVP and CRF with the hypothalamus and discusses their roles in ACTH secretion. It does not say that signals from the amygdala and locus coeruleus cause the hypothalamus to release these or other neuropeptides; the study instead examines ACTH responses to administered AVP and CRF. (LLM, conf=0.86)
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Both in human and in rat, the CRH reaction pathway is considered to be dominant in pituitary-adrenal regulation.
“Namely, both in human (39, 43–47, 55) and in rat (26, 36–38, 40, 41), CRH reaction pathway is considered to be dominant in pituitary-adrenal regulation.”
From Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis (2022) · cites this paper as [45]
The Introduction (page unavailable) calls CRF a physiologically important mediator of ACTH secretion, describes ovine CRF as a potent stimulus in humans, and cites evidence that vasopressin plays only a minor role in rats. It does not establish that the CRH pathway is dominant in both species: the Discussion (page unavailable) reports similar ACTH and cortisol responses to comparable doses of ovine CRF and vasopressin in humans and cautions that ovine and human CRF may not have identical activities. (LLM, conf=0.83)
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Authors: DeBold, C. R., Sheldon, W. R., DeCherney, G. S., Jackson, R. V., Alexander, A. N., Vale, W., Rivier, J., & Orth, D. N.
Affiliations: Vanderbilt University (US)
Salk Institute for Biological Studies (US)
ORCID: Vale, W
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1984-02-01
Volume: 73
Issue: 2
Pages: 533-538
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci111240
PMC: PMC425045
OpenAlex: W2007636157
Cited by: 189
References: 31
Citations by year: 2026: 1 · 2025: 2 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 3 · 2013: 3
FWCI: 3.88
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (2t32am007061-12)
Medical Research Council (19429)
National Health and Medical Research Council
National Cancer Institute
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: vasopressin, ACTH, ACTH release, corticotropin-releasing factor, ovine CRF, synergistic hormone interaction, cortisol, insulin-induced hypoglycemia, hypothalamic-pituitary-adrenal axis, stress response, plasma ACTH, plasma cortisol, human volunteers, dose-response relationship
MeSH terms: Adrenocorticotropic Hormone, Adult, Arginine Vasopressin, Corticotropin-Releasing Hormone, Drug Synergism, Humans, Hydrocortisone, Insulin, Kinetics, Male, Peptides, Vasopressins

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Arginine vasopressin potentiates adrenocorticotropin release induced by ovine corticotropin-releasing factor

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