Urocortin II: A Member of the Corticotropin-Releasing Factor (CRF) Neuropeptide Family that Is Selectively Bound by Type 2 CRF Receptors
Open accessAbstract
Here we describe the cloning and initial characterization of a previously unidentified CRF-related neuropeptide, urocortin II (Ucn II). Searches of the public human genome database identified a region with significant sequence homology to the CRF neuropeptide family. By using homologous primers deduced from the human sequence, a mouse cDNA was isolated from whole brain poly(A)(+) RNA that encodes a predicted 38-aa peptide, structurally related to the other known mammalian family members, CRF and Ucn. Ucn II binds selectively to the type 2 CRF receptor (CRF-R2), with no appreciable activity on CRF-R1. Transcripts encoding Ucn II are expressed in discrete regions of the rodent central nervous system, including stress-related cell groups in the hypothalamus (paraventricular and arcuate nuclei) and brainstem (locus coeruleus). Central administration of 1-10 microg of peptide elicits activational responses (Fos induction) preferentially within a core circuitry subserving autonomic and neuroendocrine regulation, but whose overall pattern does not broadly mimic the CRF-R2 distribution. Behaviorally, central Ucn II attenuates nighttime feeding, with a time course distinct from that seen in response to CRF. In contrast to CRF, however, central Ucn II failed to increase gross motor activity. These findings identify Ucn II as a new member of the CRF family of neuropeptides, which is expressed centrally and binds selectively to CRF-R2. Initial functional studies are consistent with Ucn II involvement in central autonomic and appetitive control, but not in generalized behavioral activation.
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In the hypothalamus, PFOS caused upregulation of urocortin 2, an endogenous ligand for CRFR2 that suppresses feeding behavior and inhibits gastric emptying.
“In the hypothalamus, PFOS caused upregulation of urocortin 2, an endogenous ligand for corticotropin releasing factor receptor 2 (CRFR2) that has been shown to suppress feeding behavior and inhibit gastric emptying”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Reyes et al., 2001
The Abstract identifies urocortin II as a CRF-R2-selective ligand, and the Results report that central administration reduced nighttime food intake in rats. Our copy does not report that urocortin II inhibits gastric emptying. The PFOS upregulation is the citing authors’ finding, not the point this citation is offered to support. (LLM, conf=0.87)
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“The murine Ucn II (mUcn II) gene encodes a 112–amino acid (aa) precursor containing a putative 38-aa mature peptide at the C terminus.(16) Amino acid sequences in the coding region of mUcn II show 76%, 47%, 34%, and 42% homology with human urocortin-related peptide (URP [GenBank accession No.”
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- Authors
- Reyes, T. M., Lewis, K., Perrin, M. H., Kunitake, K. S., Vaughan, J., Arias, C. A., Hogenesch, J. B., Gulyas, J., Rivier, J., Vale, W. W., & Sawchenko, P. E.
- Affiliations
- Scripps Research Institute (US)
- Laboratory of Neuronal Structure and Function and Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037; and Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037
- Corresponding author
- Vale, W. W.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-02-27
- Volume
- 98
- Issue
- 5
- Pages
- 2843-2848
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC30227
- OpenAlex
- W2095646540
- Cited by
- 887
- References
- 34
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 13 · 2023: 10 · 2022: 13 · 2021: 23 · 2020: 18 · 2019: 26 · 2018: 19 · 2017: 26 · 2016: 20 · 2015: 32 · 2014: 32 · 2013: 46 · 2012: 39
- FWCI
- 26.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation
- Fondation pour la Recherche Médicale
- National Institutes of Health (DK-26741)
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK010135, DK 26741, P01DK026741, DK-10135)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- urocortin II, corticotropin-releasing factor, CRF receptor 2, hypothalamic paraventricular nucleus, arcuate nucleus, locus coeruleus, Fos induction, nocturnal feeding, appetite regulation, autonomic regulation, neuroendocrine regulation, stress response
- MeSH terms
- CRF Receptor, Type 1, Amino Acid Sequence, Animals, Behavior, Animal, Cloning, Molecular, Corticotropin-Releasing Hormone, Cricetinae, Male, Molecular Sequence Data, RNA, Messenger, Polymerase Chain Reaction, CHO Cells, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Sequence Homology, Amino Acid, Receptors, Corticotropin-Releasing Hormone, Rats, Urocortins
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