Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (547 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A peptide of about 41 amino acids that stimulates the release of adrenocorticotropic hormone. CRH is synthesized by neurons in the paraventricular nucleus of the hypothalamus. After being released into the pituitary portal circulation, CRH stimulates the release of ACTH from the pituitary gland. CRH can also be synthesized in other tissues, such as placenta; adrenal medulla; and testis.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Corticotropin Releasing Hormone; Corticotropin-Releasing Hormone-41; Corticotropin Releasing Hormone 41; CRF-41; ACTH-Releasing Hormone; ACTH Releasing Hormone; CRF (ACTH); ACTH-Releasing Factor.
Where it fits in the MeSH classification
- Broader topics
- Pituitary Hormone-Releasing Hormones
- See also
- Receptors, Corticotropin-Releasing Hormone
Related concepts
- Adrenocorticotropic Hormone
- Paraventricular Nucleus
- Hypothalamus
- Pituitary Gland
- Placenta
- Adrenal Medulla
- Testis
Research landscape
PubMed indexes 12,879 records tagged with the MeSH heading “Corticotropin-Releasing Hormone” (counts retrieved 2026-10-31). 957 of them (7.4%) were published from 2020 onward, and the busiest period so far is through 1999 with 5,940 records.
Reviews account for 1,621 records (12.6%) and meta-analyses for 15. Randomized controlled trials number 175 (1.4%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 5,940 |
| 2000-2009 | 3,678 |
| 2010-2019 | 2,304 |
| 2020 onward | 957 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 1,621 | 12.6% |
| Meta-analyses | 15 | 0.1% |
| Randomized controlled trials | 175 | 1.4% |
Method: PubMed query "Corticotropin-Releasing Hormone"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats | 2019 | Research article Design not recorded in structured metadata | 129 | cc by PMID 30886240 · DOI · PMC6423296 |
| Stress experience and hormone feedback tune distinct components of hypothalamic CRH neuron activity | 2019 | Research article Design not recorded in structured metadata | 76 | cc by PMID 31836701 · DOI · PMC6911111 |
| Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice | 2023 | Research article Design not recorded in structured metadata | 72 | cc by PMID 36841826 · DOI · PMC9968307 |
| Androgen receptors in corticotropin-releasing hormone neurons mediate the sexual dimorphism in restraint-induced thymic atrophy | 2025 | Research article Design not recorded in structured metadata | 9 | cc by PMID 40106355 · DOI · PMC11962470 |
Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The activation of a neuronal ensemble in the central nucleus of the amygdala (CeA) during alcohol withdrawal has been hypothesized to induce high levels of alcohol drinking in dependent rats.
- Closing excerpt
- These results suggest that the CRFCeA-BNST pathway could be targeted for the treatment of excessive drinking in alcohol use disorder.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (160 words)
The activation of a neuronal ensemble in the central nucleus of the amygdala (CeA) during alcohol withdrawal has been hypothesized to induce high levels of alcohol drinking in dependent rats. In the present study we describe that the CeA neuronal ensemble that is activated by withdrawal from chronic alcohol exposure contains ~80% corticotropin-releasing factor (CRF) neurons and that the optogenetic inactivation of these CeA CRF+ neurons prevents recruitment of the neuronal ensemble, decreases the escalation of alcohol drinking, and decreases the intensity of somatic signs of withdrawal. Optogenetic dissection of the downstream neuronal pathways demonstrates that the reversal of addiction-like behaviors is observed after the inhibition of CeA CRF projections to the bed nucleus of the stria terminalis (BNST) and that inhibition of the CRFCeA-BNST pathway is mediated by inhibition of the CRF-CRF1 system and inhibition of BNST cell firing. These results suggest that the CRFCeA-BNST pathway could be targeted for the treatment of excessive drinking in alcohol use disorder.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30886240 · DOI · PMC6423296
Stress experience and hormone feedback tune distinct components of hypothalamic CRH neuron activity [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Stress leaves a lasting impression on an organism and reshapes future responses.
- Closing excerpt
- These findings reveal how stress experience and stress hormones modulate distinct components of CRH neuronal activity to mediate stress-induced adaptations.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (137 words)
Stress leaves a lasting impression on an organism and reshapes future responses. However, the influence of past experience and stress hormones on the activity of neural stress circuits remains unclear. Hypothalamic corticotropin-releasing hormone (CRH) neurons orchestrate behavioral and endocrine responses to stress and are themselves highly sensitive to corticosteroid (CORT) stress hormones. Here, using in vivo optical recordings, we find that CRH neurons are rapidly activated in response to stress. CRH neuron activity robustly habituates to repeated presentations of the same, but not novel stressors. CORT feedback has little effect on CRH neuron responses to acute stress, or on habituation to repeated stressors. Rather, CORT preferentially inhibits tonic CRH neuron activity in the absence of stress stimuli. These findings reveal how stress experience and stress hormones modulate distinct components of CRH neuronal activity to mediate stress-induced adaptations.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31836701 · DOI · PMC6911111
Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Disrupted operations of the reward circuit underlie major emotional disorders, including depression, which commonly arise following early life stress / adversity (ELA).
- Closing excerpt
- Thus, we discover a stress-sensitive, reward inhibiting BLA → NAc projection with unique molecular features, which may provide intervention targets for disabling mental illnesses.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Disrupted operations of the reward circuit underlie major emotional disorders, including depression, which commonly arise following early life stress / adversity (ELA). However, how ELA enduringly impacts reward circuit functions remains unclear. We characterize a stress-sensitive projection connecting basolateral amygdala (BLA) and nucleus accumbens (NAc) that co-expresses GABA and the stress-reactive neuropeptide corticotropin-releasing hormone (CRH). We identify a crucial role for this projection in executing disrupted reward behaviors provoked by ELA: chemogenetic and optogenetic stimulation of the projection in control male mice suppresses several reward behaviors, recapitulating deficits resulting from ELA and demonstrating the pathway's contributions to normal reward behaviors. In adult ELA mice, inhibiting-but not stimulating-the projection, restores typical reward behaviors yet has little effect in controls, indicating ELA-induced maladaptive plasticity of this reward-circuit component. Thus, we discover a stress-sensitive, reward inhibiting BLA → NAc projection with unique molecular features, which may provide intervention targets for disabling mental illnesses.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36841826 · DOI · PMC9968307
Androgen receptors in corticotropin-releasing hormone neurons mediate the sexual dimorphism in restraint-induced thymic atrophy [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Sexual dimorphism in immune responses is well documented, but the underlying mechanisms remain incompletely understood.
- Closing excerpt
- Conditional knockout of ARs in CRH neurons eliminated this sexual dimorphism, highlighting ARs in CRH neurons as pivotal regulators of sex-specific immune responses to stress.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (100 words)
Sexual dimorphism in immune responses is well documented, but the underlying mechanisms remain incompletely understood. Here, we identified a subset of corticotropin-releasing hormone (CRH) neurons that express androgen receptors (ARs) as key mediators of sex differences in restraint-induced immunosuppression. Mechanistically, androgens directly activate AR-positive CRH neurons, enhancing the hypothalamic-pituitary-adrenal axis activation. This results in elevated corticosterone levels in response to restraint stress, leading to increased immune cell apoptosis and immune organ atrophy in male mice. Conditional knockout of ARs in CRH neurons eliminated this sexual dimorphism, highlighting ARs in CRH neurons as pivotal regulators of sex-specific immune responses to stress.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40106355 · DOI · PMC11962470
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress [5]
- Research article The role of corticotropin-releasing factor in depression and anxiety disorders [6]
- Research article Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress [7]
- Research article Corticotropin-releasing factor, norepinephrine, and stress [8]
- Research article Variations in maternal care in infancy regulate the development of stress reactivity [9]
- Research article Corticotropin releasing factor receptors and their ligand family [10]
References
- de Guglielmo G, Kallupi M, Pomrenze MB, Crawford E, Simpson S, Schweitzer P, et al.. Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats. . 2019. PMID 30886240 · DOI · PMC6423296
- Kim JS, Han SY, Iremonger KJ. Stress experience and hormone feedback tune distinct components of hypothalamic CRH neuron activity. . 2019. PMID 31836701 · DOI · PMC6911111
- Birnie MT, Short AK, de Carvalho GB, Taniguchi L, Gunn BG, Pham AL, et al.. Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice. . 2023. PMID 36841826 · DOI · PMC9968307
- Meng Y, Li Y, Gu H, Chen Z, Cui X, Wang X. Androgen receptors in corticotropin-releasing hormone neurons mediate the sexual dimorphism in restraint-induced thymic atrophy. . 2025. PMID 40106355 · DOI · PMC11962470
- Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002. PMID 12377295 · DOI
- Arborelius L, Owens MJ, Plotsky PM, Nemeroff CB. The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol. 1999. PMID 9854171 · DOI
- Slominski A, Wortsman J, Luger T, Paus R, Solomon S. Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Physiol Rev. 2000. PMID 10893429 · DOI
- Koob GF. Corticotropin-releasing factor, norepinephrine, and stress. Biol Psychiatry. 1999. PMID 10560023 · DOI
- Caldji C, Diorio J, Meaney MJ. Variations in maternal care in infancy regulate the development of stress reactivity. Biol Psychiatry. 2000. PMID 11137058 · DOI
- Perrin MH, Vale WW. Corticotropin releasing factor receptors and their ligand family. Ann N Y Acad Sci. 1999. PMID 10816663 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.