Cited by 257Neuropeptides and Animal PhysiologyStress Responses and CortisolNeuroendocrine regulation and behavior

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Corticotropin-Releasing Factor (CRF) and Endocrine Responses to Stress: CRF Receptors, Binding Protein, and Related Peptides

Turnbull, A. V., Rivier, C.·1997·Experimental Biology and Medicine

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Abstract

Corticotropin-releasing factor (CRF) is a 41-amino acid neuropeptide, which is recognized as a critical mediator of complimentary, stress-related endocrine, autonomic, and behavioral responses in mammalian species. CRF belongs to a family of structurally related peptides including frogskin sauvagine and fish urotensin I. The effects of CRF and related peptides are mediated by two distinct receptors, which differ in their anatomical distribution, as well as in their pharmacological characteristics. In addition, CRF is bound with high affinity by a CRF binding protein (CRF-BP), which is a putative inhibitor of CRF action. CRF is probably not the sole endogenous ligand for CRF receptors or the CRF-BP, since a second mammalian member of the CRF family, urocortin, has recently been identified. This article describes recent findings with respect to CRF, its receptors, binding protein, and CRF-related peptides, which provide further insights into the role and mechanisms of CRF action in stress responses.

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Endocrinology of Complex Life Cycles
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Central CRF inhibits gastric emptying of a nutrient solid meal in rats: the role of CRF2receptors
Martı́nez, V., Barquist, E. S., Rivier, J., & Taché, Y. (1998) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1998.274.5.g965 · Cited by 81
Anorectic actions of prolactin-releasing peptide are mediated by corticotropin-releasing hormone receptors
Lawrence, C. B., Liu, Y.-L., Stock, M. J., & Luckman, S. M. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00402.2003 · Cited by 76
“There are several CRH receptor subtypes described to date; CRH receptor type 1 and CRH receptor type 2, which can exist as several splice variants, see (37, 56).”
Background
From Hans Selye's Discovery of Biological Stress to the Identification of Corticotropin‐ Releasing Factor Signaling Pathways
Taché, Y., & Brunnhuber, S. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1410.007 · Cited by 76
Expression and hypophysiotropic actions of corticotropin-releasing factor in Xenopus laevis
Boorse, G. C., & Denver, R. J. (2004) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2004.04.001 · Cited by 74
“CRF was Wrst isolated for its ability to stimulate ACTH secretion in mammals (Turnbull and Rivier, 1997; Vale et al., 1981) and regulation of ACTH by CRF is considered to be the primary hypophysiotropic role for this peptide (Vale et al., 1997).”
Background
Peripheral CRF activates myenteric neurons in the proximal colon through CRF1receptor in conscious rats
Miampamba, M., Maillot, C. L., Million, M., et al. (2002) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00434.2001 · Cited by 74
Regulation of Synaptic Transmission by CRF Receptors
Orozco-Cabal, L. F., Pollandt, S., Liu, J., Shinnick‐Gallagher, P., & Gallagher, J. P. (2006) · Reviews in the Neurosciences · doi:10.1515/revneuro.2006.17.3.279 · Cited by 73
Stress and addiction: contribution of the corticotropin releasing factor (CRF) system in neuroplasticity
Haass‐Koffler, C. L., & Bartlett, S. E. (2012) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2012.00091 · Cited by 74
“, 1955) where it stimulates glucocorticoid synthesis and secretion form the adrenal cortex (Turnbull and Rivier, 1997).”
Background
Corticotropin‐releasing factor binding protein within the ventral tegmental area is expressed in a subset of dopaminergic neurons
Wang, H., & Morales, M. (2008) · The Journal of Comparative Neurology · doi:10.1002/cne.21751 · Cited by 70
“It has been hypothesized that interactions between CRF and membrane-associated CRF-BP in the brain are important in maintaining synaptic CRF concentrations (Turnbull and Rivier, 1997).”
Background
Distribution and expression of CRF receptor 1 and 2 mRNAs in the CRF over-expressing mouse brain
Kőrösi, A., Veening, J. G., Kozicz, T., Henckens, M. J. A. G., Dederen, J., Groenink, L., van der Gugten, J., Olivier, B., & Roubos, E. W. (2006) · Brain Research · doi:10.1016/j.brainres.2005.12.034 · Cited by 72
“The E – WN Ucn1 acts through both CRF1 and CRF2 receptors but has a strong preference for CRF2 (Potter et al., 1994; Turnbull and Rivier, 1997; Reul and Holsboer, 2002).”
Stress neuropeptides evoke epithelial responses via mast cell activation in the rat colon
Santos, J., Yates, D. A., Guilarte, M., Vicario, M., Alonso, C., & Perdue, M. H. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.07.002 · Cited by 68
Interleukin-6 is an afferent signal to the hypothalamo-pituitary-adrenal axis during local inflammation in mice
Turnbull, A. V., Prehar, S., Kennedy, A. R., Little, R. A., & Hopkins, S. J. (2003) · Endocrinology · doi:10.1210/en.2002-220964 · Cited by 66
“Although AVP is able to induce ACTH secretion and is also released in the pituitary by neurons direct from the PVN, CRF is considered to constitute the major ACTH secretagogue in rodents (1).”
BackgroundSelf-citation
Stress hormones mediate developmental plasticity in vertebrates with complex life cycles
Denver, R. J. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100301 · Cited by 73
Is It Really a Matter of Simple Dualism? Corticotropin-Releasing Factor Receptors in Body and Mental Health
Janssen, D., & Kozicz, T. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00028 · Cited by 65
“Upon exposure to a stressor, the HPA-axis is activated by the release of CRF into portal vessels and subsequently acts upon the CRFR1 located in the anterior pituitary (Turnbull and Rivier, 1997; Vale et al., 1997).”
Background
Sequences, expression patterns and regulation of the corticotropin-releasing factor system in a teleost
Chen, C., & Fernald, R. D. (2008) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2008.04.003 · Cited by 63
“In addition to its well studied effects in mediating the whole body stress response, CRF influences a wide spectrum of processes in both the central nervous system and in the periphery, underscoring its role in integrating diverse physiological systems in mammals (Turnbull and Rivier, 1997; Bale and Vale, 2004).”
Background
Urocortin in the ventromedial hypothalamic nucleus acts as an inhibitor of feeding behavior in rats
Ohata, H., Suzuki, K. S., Oki, Y., & Shibasaki, T. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02378-1 · Cited by 64
Urocortins of the South African Clawed Frog, Xenopus laevis: Conservation of Structure and Function in Tetrapod Evolution
Boorse, G. C., Crespi, E. J., Dautzenberg, F. M., & Denver, R. J. (2005) · Endocrinology · doi:10.1210/en.2005-0497 · Cited by 61
“C factor (CRF) was first isolated from the sheep hypothalamus as a potent secretagogue for pituitary ACTH (1) and has since been shown to mediate endocrine, autonomic, behavioral, and immune responses to stress (2).”
Background
Fetal adaptation to stress
Amiel‐Tison, C., CABROL, D., Denver, R. J., Jarreau, P., Papiernik, E., & Piazza, P. V. (2004) · Early Human Development · doi:10.1016/j.earlhumdev.2004.03.007 · Cited by 59
“CRH is a 41amino-acid polypeptide first isolated for its ability to stimulate ACTH secretion in mammals [33,34].”
Background
Chronic Pain and Comorbid Emotional Disorders: Neural Circuitry and Neuroimmunity Pathways
Li, M. H., She, K., Zhu, P., Li, Z., Liu, J., Luo, F., & Ye, Y. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26020436 · Cited by 70
“CRH and its receptors are located in many areas of the brain outside the hypothalamus, including parts of the limbic system, as well as in the brainstem and spinal cord’s central arousal sympathetic system (LC/NE) [25].”
Single exposure to social defeat increases corticotropin-releasing factor and glucocorticoid receptor mRNA expression in rat hippocampus
Marini, F., Pozzato, C., Andreetta, V., Jansson, B., Arban, R., Domenici, E., & Carboni, L. (2005) · Brain Research · doi:10.1016/j.brainres.2005.10.002 · Cited by 57
Urocortin in the synovial tissue of patients with rheumatoid arthritis
Uzuki, M., Sasano, H., Muramatsu, Y., Totsune, K., Takahashi, K., Oki, Y., Iino, K., & Sawai, T. (2001) · Clinical Science · doi:10.1042/cs1000577 · Cited by 57
The Activation of Urocortin Immunoreactive Neurons in the Edinger-Westphal Nucleus Following Acute Pain Stress in Rats
Kozicz, T., Li, M., & Areviura, A. (2001) · Stress · doi:10.3109/10253890109115724 · Cited by 58
Urocortin Is Not a Significant Regulator of Intermittent Electrofootshock-Induced Adrenocorticotropin Secretion in the Intact Male Rat**This work was supported by NIH Grant DK-26741 and The Foundation for Research.
Turnbull, A. V., Vaughan, J. M., Rivier, J., Vale, W., & RIVIER, C. L. (1999) · Endocrinology · doi:10.1210/endo.140.1.6419 · Cited by 58
“CRF belongs to a family of structurally related peptides, including amphibian sauvagine and piscine urotensin I (4, 5).”
Self-citation
Corticotropin-releasing factor receptor type 1 and type 2 interaction in irritable bowel syndrome
Nozu, T., & Okumura, T. (2015) · Journal of Gastroenterology · doi:10.1007/s00535-015-1086-8 · Cited by 59
“Stress induces behavioral, neuroendocrine, and autonomic responses, and corticotropin-releasing factor (CRF) is the main mediator of these responses in the brain–gut axis [7–13].”
Background
Urocortin and Corticotropin-Releasing Factor Receptor Expression in Normal Cycling Human Ovaries1
Muramatsu, Y., Sugino, N., SUZUKI, T. A., Totsune, K., Takahashi, K., Tashiro, A., Hongo, M., Oki, Y., & Sasano, H. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.3.7299 · Cited by 60
Corticotropin-releasing factor receptor 1-deficient mice do not develop postoperative gastric ileus
Luckey, A. E., Wang, L., Jamieson, P. M., Basa, N. R., Million, M., Czimmer, J., Vale, W., & Taché, Y. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)01069-2 · Cited by 56
Colitis induces CRF expression in hypothalamic magnocellular neurons and blunts CRF gene response to stress in rats
Kresse, A. E., Million, M., Saperas, E., & Taché, Y. (2001) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2001.281.5.g1203 · Cited by 56
“CORTICOTROPIN-RELEASING FACTOR (CRF) is the primary mediator of the hypothalamic pituitary-adrenal (HPA) endocrine limb of the stress response (50, 53, 54).”
Background

Authors: Turnbull, A. V., & Rivier, C.
Affiliations: Salk Institute for Biological Studies (US)
Venue: Experimental Biology and Medicine
Publisher: Frontiers Media SA
Published: 1997-05-01
Volume: 215
Issue: 1
Pages: 1-10
ISSN: 0071-3384 (ISSN-L)
1535-3702
1535-3699
DOI: 10.3181/00379727-215-44108
OpenAlex: W2334462456
Cited by: 256
References: 0
Citations by year: 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 7 · 2015: 2 · 2014: 9 · 2013: 10 · 2012: 13
FWCI: 6.42
Type: journal article
Language: en
Open access: closed
Locations: Experimental Biology and Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (R01MH051774, NIMH51774)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDDK-26741)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD013527, NICHD-13527)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
Keywords: corticotropin-releasing factor, CRF receptors, CRF-binding protein, urocortin, stress response, endocrine stress response, sauvagine, urotensin I, neuropeptides, autonomic stress response, behavioral stress response
MeSH terms: Adrenocorticotropic Hormone, Amino Acid Sequence, Animals, Carrier Proteins, Corticotropin-Releasing Hormone, Humans, Luteinizing Hormone, Molecular Sequence Data, Neuropeptides, Stress, Physiological, Receptors, Corticotropin-Releasing Hormone

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Corticotropin-Releasing Factor (CRF) and Endocrine Responses to Stress: CRF Receptors, Binding Protein, and Related Peptides

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