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Cited by 71Stress Responses and CortisolAdrenal Hormones and DisordersNeuropeptides and Animal Physiology

Effect of synthetic ovine corticotropin-releasing factor: prolonged duration of action and biphasic response of plasma adrenocorticotropin and cortisol

DEBOLD, C. ROWAN, DECHERNEY, G. STEPHEN, JACKSON, RICHARD V., SHELDON, WILLIAM R., ALEXANDER, A. NANCYE, ISLAND, DONALD P., RIVIER, JEAN, VALE, WYLIE +1 more·1983·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem-57-2-294
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Abstract

The duration of the response to synthetic ovine corticotropin-releasing factor (CRF) was studied in 13 healthy male volunteer subjects. Placebo or CRF (0.3, 3, or 30 micrograms/kg BW) was administered as an iv bolus or, in the case of the largest dose, a 30-sec infusion in single blind fashion in the late afternoon. Basal plasma immunoreactive ACTH (IR-ACTH) and IR-cortisol were 10.8 +/- 7.7 pg/ml and 5.0 +/- 1.8 micrograms/dl (mean +/- SD), respectively. IR-ACTH rose rapidly after CRF, reached an initial peak at 15 min, fell rapidly until 1.5 h after CRF, and then either fell more slowly (after the lowest dose) or rose to a second major peak at 2-3 h before falling back to baseline. After 0.3, 3, and 30 micrograms/kg CRF, IR-ACTH remained elevated for 4, 7, and 8 h, respectively. The effect on plasma IR-cortisol was similar, but more prolonged. The magnitude of both peaks of IR-ACTH, the duration of the response, and the area under the curve all appeared dose dependent. The same was true for IR-cortisol, except that the first peak height was similar after all three doses. The duration of CRF's action is probably due to its long circulating half-life. The biphasic response curve may reflect initial secretion of a readily releasable pool of ACTH, followed by later secretion of a second pool of newly synthesized and/or matured peptide. The next morning's normal circadian rise in both IR-ACTH and IR-cortisol was delayed and diminished after 3 micrograms/kg CRF; there was no increase in IR-ACTH after 30 micrograms/kg CRF, and the IR-cortisol level was diminished. Inhibition of the normal circadian rise may reflect inhibition of ACTH secretion by the sustained high plasma cortisol levels.

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Crossref · 10.1210/jcem-57-2-294

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Authors
DEBOLD, C. R., DECHERNEY, G. S., JACKSON, R. V., SHELDON, W. R., ALEXANDER, A. N., ISLAND, D. P., RIVIER, J., VALE, W., & ORTH, D. N.
Affiliations
Salk Institute for Biological Studies (US)
ORCID
VALE, WYLIE
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
1983-08
Volume
57
Issue
2
Pages
294-298
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem-57-2-294
OpenAlex
W2007115794
Cited by
71
References
16
Citations by year
2026: 1 · 2024: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 5 · 2016: 1 · 2014: 2 · 2013: 1 · 2012: 1
FWCI
3.55
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ca011685-21, 5r25ca019429-11)
  • National Center for Research Resources (M01RR000095)
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, ovine CRF, ACTH secretion, cortisol, duration of action, dose-response relationship, circadian rhythm, glucocorticoid negative feedback
MeSH terms
Adrenocorticotropic Hormone, Adult, Corticotropin-Releasing Hormone, Dose-Response Relationship, Drug, Drug Evaluation, Humans, Hydrocortisone, Kinetics, Male, Peptides

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