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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Items 101–200 of 257

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“…regions contain higher levels of CRFR1 than CRFR2 receptors, and one would expect stronger or equal effects of CRF than Ucn1 in these brain regions (Potter et al., 1994, Chalmers et al., 1995, Perrin et al., 1995, Turnbull and Rivier, 1997, Steckler and Holsboer, 1999, Fekete and Zorrilla, 2006).”
Background
Peripheral Injection of a New Corticotropin-Releasing Factor (CRF) Antagonist, Astressin, Blocks Peripheral CRF- and Abdominal Surgery-Induced Delayed Gastric Emptying in Rats
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“pituitary adrenocorticotropin (ACTH) release is mediated primarily by CRF-R1 and the recent use of CRF-R1 knockout mice (Turnbull and Rivier, 1997; Smith et al., 1998; Timpl et al., 1998).”
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“Although CRF is best known as the hypothalamic neuropeptide that governs the endocrine stress response [37], its distribution and actions in the CNS suggest a broad involvement in integrating hormonal, autonomic, and behavioral adaptations [38–41].”
Background
Corticotropin‐releasing factor, urocortin 1, and their receptors in the mouse spinal cord
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“Release of ACTH into the bloodstream is dependent upon activation of corticotrophin-releasing hormone (CRH) receptors on pituitary corticotrophs (Turnbull and Rivier, 1997).”
Background
Functional expression of corticotropin‐releasing hormone (CRH) receptor 1 in cultured rat microglia
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“…West Warwick, RI) and were mediated through an action on CRH1 or CRH2 receptors continuously monitored using a polygraph (Model 12RX, (but see Turnbull & Rivier, 1997 [11]; they suggest a Grass Instruments, West Warwick RI) for the duration of CRH2 receptor mechanism), or whether the…”
Method
Identification of urocortin mRNA and peptide in the human endometrium
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“In fact, CRF and urocortin stimulate pituitary proopiomelanocortin (POMC) gene expression (Vaughan et al. 1995, Turnbull and Rivier 1997, Asaba et al. 1998, Hsu and Hsueh 2001).”
Background
Corticotropin-releasing factor-binding protein (CRF-BP) inhibits CRF- and urotensin-I-mediated activation of CRF receptor-1 and -2 in common carp
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“It is thought to prevent unwanted ACTH (adrenocorticotropic hormone) release from the pituitary gland in response to high levels of circulating placenta-derived CRF (Behan et al., 1989; Orth and Mount, 1987).”
Background
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“These neuropeptides include CRH, mainly involved in the activation of the hypothalamo-pituitary-adrenal axis, and known to inhibit energy intake (47).”
Background
Biochemical characterization and expression analysis of the Xenopus laevis corticotropin-releasing hormone binding protein
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“The prevailing view is that CRH-BP modulates CRH biological activity by binding the peptide with high affinity, thus preventing its interaction with the CRH receptors (Linton et al., 1990; Turnbull and Rivier, 1997; Zhao et al., 1997).”
Background
Distribution of urocortin‐like immunoreactivity in the central nervous system of the frog Rana esculenta
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“…Ucn possesses biological activities similar to those of CRF and urotensin I, and, like CRF, it plays an important role in modifying the efferent components of endocrine, autonomic, immune, and behavioral responses to stress (Turnbull et al., 1996; Turnbull and Rivier, 1997; Skelton et al., 2000b).”
Background
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“…implications of CRF–NPS interactions in the brain stem Release of CRF is an initial step of a neuroendocrine cascade during activation of the hypothalamic–pituitary–adrenal (HPA) axis, which typically mediates physiological responses to stress (Turnbull & Rivier, 1997; Bale & Vale, 2004).”
Background
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“For example, whereas oCRF, Ac-oCRF and oCRF(4-41) were equipotent in the rat dispersed anterior pituitary cell culture assay, oCRF(6-41) and oCRF(7-41) had 11% and 0.”
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“Urocortin exerts physiological/pharmacological effects similar to those produced by CRH, including the stimulation of ACTH release from the anterior pituitary (Turnbull and Rivier 1997).”
Background
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“The anti-UCN1 serum had been generated in rabbits against rat UCN1 coupled by glutaraldehyde to human aglobulin , and the high specificity of the antiserum has been demonstrated [2] [40].”
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“CRF and urocortin are bound by CRF-BP, a 37 kDa protein that binds both peptides with an affinity equal to or greater than the CRF receptors (101).”
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“It is released by neurons in the paraventricular nucleus of the hypothalamus to regulate pituitary ACTH secretion, thus triggering a key component of the hypothalamic-pituitary-adrenal (HPA) axis [6].”
Background
A corticotropin-releasing hormone antisense oligodeoxynucleotide reduces spontaneous waking in the rat
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“[9,25]).”
Background
Fos induction in selective hypothalamic neuroendocrine and medullary nuclei by intravenous injection of urocortin and corticotropin-releasing factor in rats
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“Activation of CRF Signaling CRF expression is upregulated in the hypothalamus and the peptide released into the median eminence under conditions of stress leading to pituitary ACTH and subsequently adrenal glucocorticoid hormone release (cortisol in humans and corticosterone in rodents) (Turnbull and Rivier, 1997; Smi…”
BackgroundMethodInfluential
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Self-citation
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“Even though, CRH-R1 expression in the PVN is up-regulated in several stressful conditions supposedly by CRH released into the PVNwhich in turn up-regulates PVN-CRH expression (Mansi et al., 1996; Imaki et al., 1996; Turnbull and Rivier, 1997), the mRNA levels of this receptor were unchanged.”
PRINCIPLES OF PSYCHONEUROENDOCRINOLOGY
Campeau, S., Day, H. E. W., Helmreich, D. L., Kollack‐Walker, S., & Watson, S. J. (1998) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70004-6 · Cited by 31
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“…of ACTH secretion are maintained in the absence of CRH, pharmacological studies and experiments with CRH and CRH receptor knock out mice have demonstrated that the peptide is indispensable for the responses to stress (Turnbull & Rivier, 1997; Venihaki & Majzoub, 1999; Turnbull, et al., 1999).”
Background
Water avoidance stress activates colonic myenteric neurons in female rats
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“These neurons release CRF into the hypophyseal portal blood which, in turn, activates CRF1 receptors located on the corticotroph cells in the anterior pituitary resulting in adrenocorticotropic hormone and bendorphin secretion and adrenal corticosterone release [14].”
Background
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“Urocortin stimulates pituitary POMC gene expression[23,24,32] , and because the endometrium also expresses and secretes POMC [33] and -endorphin [34], urocortin may stimulate endometrial POMC-derived peptide secretion, as in placenta [30] and in the pituitary [23,24,32] .”
Background
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Self-citation
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“Previous studies demonstrated that CRF and UCN I stimulate the HPA axis in rodents by activating CRFR1, which are expressed abundantly in the central nervous system (CNS), especially in the cerebral cortex and the anterior pituitary (Skelton et al., 2000; Turnbull and Rivier, 1997; Vale et al., 1981; Vaughan et al., 1…”
Background
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“The effect of central administration of UCN I mimicks the effect of central administration of CRF, characterised by endocrine, autonomic and behavioral stress responses (Koob and Heinrichs, 1999; Turnbull and Rivier, 1997).”
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“14 37 To date, two distinct CRF receptor subtypes, CRF 1 and CRF 2 , have been cloned and characterised from rat and human brains.”
Background
The effect of urocortin on ingestive behaviours and brain Fos immunoreactivity in mice
Sinnayah, P., Blair-West, J. R., McBurnie, M. I., McKinley, M. J., Oldfield, B. J., Rivier, J., Vale, W., Walker, L., Weisinger, R. S., & Denton, D. A. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02760.x · Cited by 23
“Two of the main effects of UCN, i.e. stimulation of ACTH release and stimulation of sympathetic nervous system activity (Spina et al., 1996; Turnbull & Rivier, 1997; De Fanti & Martinez, 2002) are known to stimulate sodium intake (Denton et al., 1999; Thunhorst et al., 1996).”
BackgroundInfluential
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“Although corticotropin-releasing factor (CRF) is best recognized as the hypothalamic neuropeptide that governs the endocrine stress response [30, 31], its distribution and actions in the CNS are similar to that of a neuromodulator/neurotransmitter [32–34].”
Background
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“CRF in the paraventricular nucleus of the hypothalamus controls the pituitary adrenal response to stress (2).”
Background
Modulation of Sleep Homeostasis by Corticotropin Releasing Hormone in REM Sleep-Deprived Rats
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Neuroprotective Effects of the CRF 1 Antagonist R121920 after Permanent Focal Ischemia in the Rat
Mackay, K. B., Bozigian, H. P., Grigoriadis, D. E., Loddick, S. A., Verge, G. M., & Foster, A. C. (2001) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200110000-00009 · Cited by 21
“…is responsible for the release of ACTH, and CRF1 receptor–selective antagonists inhibit the elevations of ACTH and corticosterone that are provoked by CRF administration and stress (Chalmers et al., 1996; De Souza, 1995; Dunn and Berridge 1990; Perrin and Vale, 1999; Turnbull and Rivier, 1997).”
Background
Corticotropin-releasing hormone inhibits lowering of interstitial pressure in rat trachea after neurogenic inflammation
Gjerde, E.-A. B., Woie, K., Wei, E. T., & Reed, R. K. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(98)00403-8 · Cited by 20
Effect of inescapable stress in rodent models of depression and posttraumatic stress disorder on CRH and vasopressin immunoreactivity in the hypothalamic paraventricular nucleus
Mironova, V. I., Rybnikova, E. A., & Пивина, С. Г. (2013) · Acta Physiologica Hungarica · doi:10.1556/aphysiol.100.2013.4.4 · Cited by 20
An acute increase in water temperature can increase free amino acid concentrations in the blood, brain, liver, and muscle in goldfish (Carassius auratus)
Wang, Y., Han, G., Pham, C. V., Koyanagi, K., Song, Y., Sudo, R., Lauwereyns, J., Cockrem, J. F., Furuse, M., & Chowdhury, V. S. (2019) · Fish Physiology and Biochemistry · doi:10.1007/s10695-019-00642-5 · Cited by 21
Binge Eating in Female Rats Induced by Yo-Yo Dieting and Stress
Cifani, C., Bonaventura, M. V. M. D., Ciccocioppo, R., & Massi, M. (2012) · Neuromethods · doi:10.1007/978-1-62703-104-2_3 · Cited by 21
Cocaine- and Amphetamine-Regulated Transcript (CART) Peptide Plays Critical Role in Psychostimulant-Induced Depression
Qing, M., Kim, H., Oh, S., Lee, Y., Hu, Z., & Oh, K. (2018) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2018.141 · Cited by 20
“The HPA axis is composed of three major structures: the paraventricular nucleus of the hypothalamus, the anterior lobe of the pituitary gland, and the adrenal gland (Turnbull and Rivier, 1997; Zuloaga et al., 2015).”
Background
Separate Locations of Urocortin and its Receptors in Mouse Testis: Function in Male Reproduction and the Relevant Mechanisms
Tao, J., Lin, M. T., Sha, J., et al. (2007) · Cellular Physiology and Biochemistry · doi:10.1159/000100649 · Cited by 19
Hypothalamic-Pituitary-Adrenal Axis
Kyrou, I., & Tsigos, C. (2005) · Springer eBooks · doi:10.1007/3-540-26861-8_3 · Cited by 20
Substance induced plasticity in noradrenergic innervation of the paraventricular hypothalamic nucleus
Jansen, A. S. P., Schmidt, E. D., Voorn, P., & Tilders, F. J. H. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02453.x · Cited by 19
Neuroimmunotoxicology: Modulation of neuroimmune networks by toxicants
Pabello, N. G., & Lawrence, D. A. (2006) · Clinical Neuroscience Research · doi:10.1016/j.cnr.2006.04.004 · Cited by 18
Corticotropin-releasing factor: A possible key to gut dysfunction in the critically ill
Hill, L. T., Kidson, S. H., & Michell, W. L. (2013) · Nutrition · doi:10.1016/j.nut.2012.12.023 · Cited by 19
“CRF, however, also is expressed throughout several other brain regions of mammals suggesting that there are a variety of functions of this molecule [9].”
Background
Prenatal Stress Alters Progestogens to Mediate Susceptibility to Sex-Typical, Stress-Sensitive Disorders, such as Drug Abuse: A Review
Frye, C. A., Paris, J. J., Osborne, D. M., Campbell, J. C., & Kippin, T. E. (2011) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2011.00052 · Cited by 18
Transient Anosmia Induces Depressive-like and Anxiolytic-like Behavior and Reduces Amygdalar Corticotropin-Releasing Hormone in a ZnSO4-Induced Mouse Model
Ahn, S., Choi, M., Kim, H.-J., Yang, E., Mahmood, U., Kang, S.-I., Kim, D. W., Kim, H.-S., & Kim, H.-S. (2018) · Chemical Senses · doi:10.1093/chemse/bjy008 · Cited by 17
Intravenous injection of urocortin 1 induces a CRF2 mediated increase in circulating ghrelin and glucose levels through distinct mechanisms in rats
Wang, L., Stengel, A., Goebel‐Stengel, M., et al. (2012) · Peptides · doi:10.1016/j.peptides.2012.11.009 · Cited by 16
“While the CRF1 signaling system in the brain is well established to orchestrate the endocrine, behavioral, and visceral responses to stress [27,43,48], growing anatomical and physiological evidence also supports an important role of the peripheral CRF2 signaling system within the viscera, namely the gut and heart [12,…”
Background
Expression of urocortin and its receptors in the rat epididymis
Luca, A. D., Liguori, G., Squillacioti, C., et al. (2014) · Reproductive Biology · doi:10.1016/j.repbio.2014.01.007 · Cited by 16
Sickness and satiety: Physiological mechanisms underlying perceptions of nausea and stomach fullness
Levine, M. E. (2005) · Current Gastroenterology Reports · doi:10.1007/s11894-005-0020-2 · Cited by 16
Localisation and Physiological Regulation of Corticotrophin‐Releasing Factor Receptor 1 mRNA in theXenopus laevisBrain and Pituitary Gland
Calle, M., Jenks, B. G., Corstens, G. J. H., et al. (2006) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2006.01475.x · Cited by 16
The Effect of Exercise on the Hypothalamic-Pituitary-Adrenal Axis
St-Pierre, D. H., & Richard, D. (2020) · Contemporary Endocrinology · doi:10.1007/978-3-030-33376-8_3 · Cited by 17
Sensitivity and Resilience to Predator Stress-Enhanced Ethanol Drinking Is Associated With Sex-Dependent Differences in Stress-Regulating Systems
Alavi, M., Ryabinin, A. E., Helms, M. L., Nipper, M. A., Devaud, L. L., & Finn, D. A. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.834880 · Cited by 15
“In contrast to the mPFC, PS-enhanced drinking was not associated with changes in “sensitive” mice, but with sex-independent decreases in CRF-R1, CRF-R2, and GR in “resilient” mice.”
BackgroundInfluential
Design, synthesis and structure–affinity relationships of 4-methylidenepiperidine and 4-aryl-1,2,3,6-tetrahydropyridine derivatives as corticotropin-releasing factor1 receptor antagonists
Nakazato, A., Kumagai, T., Okubo, T., et al. (2000) · Bioorganic & Medicinal Chemistry · doi:10.1016/s0968-0896(00)00045-6 · Cited by 15
Genomic organization and tissue-specific expression of rat urocortin
Park, J., Lee, Y.-J., Na, S.-Y., & Kim, K. L. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01434-8 · Cited by 14
The effects of corticotropin-releasing factor and the urocortins on hypothalamic gamma-amino butyric acid release – The impacts on the hypothalamic–pituitary–adrenal axis
Bagosi, Z., Csabafi, K., Jászberényi, M., & Telegdy, G. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.01.007 · Cited by 13
“CRF binds to CRFR1 with higher affinity than to CRFR2, and UCN1 activates CRFR1 and CRFR2 with equal potencies, both being inactivated by CRFR-BP (Turnbull and Rivier, 1997).”
Background
Chapter 2. Recent Progress in Corticotropin-Releasing Factor Receptor Agents
McCarthy, J. R., Heinrichs, S. C., & Grigoriadis, D. E. (1999) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)60564-3 · Cited by 13
Central Corticotropin-Releasing Factor and the Hypothalamic-Pituitary-Adrenal Axis in Gastrointestinal Physiology
Taché, Y., & Million, M. (2006) · Elsevier eBooks · doi:10.1016/b978-012088394-3/50033-7 · Cited by 12
The Use of Frogskin as a Biological Dressing for Temporary Cover of Burn Wounds
Piccolo, N. S., Piccolo, M. S., & Piccolo, M. T. S. (2007) · Springer eBooks · doi:10.1007/978-3-540-46326-9_16 · Cited by 12
Monkey corticotropin-releasing factor1 receptor: Complementary DNA cloning and pharmacological characterization
Oshida, Y., Ikeda, Y., Chaki, S., et al. (2003) · Life Sciences · doi:10.1016/j.lfs.2003.08.035 · Cited by 12
Urocortins and their unfolding role in mammalian social behavior
Wagner, S. (2018) · Cell and Tissue Research · doi:10.1007/s00441-018-2962-3 · Cited by 10
The hypothalamic-pituitary-adrenal (HPA) axis: A major mediator of the adaptive responses to stress
Gabry, K. E., Chrousos, G. P., & Gold, P. W. (2003) · Neuroimmune biology · doi:10.1016/s1567-7443(03)80055-8 · Cited by 12
Functional and Anatomical Characterization of Corticotropin-Releasing Factor Receptor Subtypes of the Rat Spinal Cord Involved in Somatic Pain Relief
Mousa, S. A., Shaqura, M. A., Khalefa, B. I., Li, L., Al-Madol, M. A., Treskatsch, S., & Schäfer, M. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02481-z · Cited by 8
Distribution of type I corticotropin‐releasing factor (CRF1) receptors on GABAergic neurons within the basolateral amygdala
Calakos, K. C., Blackman, D. R., Schulz, A. M., & Bauer, E. P. (2016) · Synapse · doi:10.1002/syn.21953 · Cited by 9
“Released by the paraventricular nucleus of the hypothalamus (PVN), it triggers a key component of the hypothalamic–pituitary–adrenal axis (Turnbull & Rivier, 1997).”
Role of Secretin Peptide Family and their Receptors in the Hypothalamic Control of Energy Homeostasis
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Stress and Reproduction in Mammals
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Comparative distribution of urocortin- and CRF-like immunoreactivities in the nervous system of the earthworm Lumbricus terrestris
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Effect of central urocortin on carbon tetrachloride-induced acute liver injury in rats
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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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