Expression of corticotropin releasing hormone receptors type I and type II mRNA in suicide victims and controls
Abstract
Corticotropin-releasing hormone (CRH) is a key neuroendocrine factor implementing endocrine, immune and behavioral responses to stress. CRH exerts its action through two major receptors, CRH-R1 and CRH-R2. Recently novel non-peptidic antagonists directed against CRH-R1 or CRH-R2 have been proposed as promising agents in the treatment of depression, anxiety and eating disorder. However, so far the CRH-receptor system has not been widely studied in humans. Therefore, we employed quantitative TaqMan PCR to analyze the expression and distribution of both CRH-R1 and CRH-R2 in human brain tissue and peripheral organs. Furthermore the expression of CRH receptors was analyzed for the first time in pituitaries of suicide victims by in situ hybridization and quantitative PCR. Our data demonstrated a different expression pattern in humans as compared to rodents. Both CRH-R1 and CRH-R2 were expressed in high amounts in the brain with the strongest expression in the pituitary. As described in rodents, however the CRH-R1 in human was the predominant receptor in the brain (82.7 +/- 11.0%), whilst CRH-R2 was the predominant receptor in peripheral organs (77.0 +/- 15.8%). There was a shift in the ratio of CRH-R1/R2 in the pituitaries of suicide victims. In conclusion, both CRH-R1 and CRH-R2 are widely expressed in human tissues with a distribution substantially different from rodents. Strong expression of both CRH-R1 and CRH-R2 in human pituitaries suggests that particularly under stress, activation of the HPA axis can be maintained through both receptors.
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Hiroi et al. found hyperplastic adrenals in suicide victims, corroborating such hypothesis.
“Hiroi et al. found hyperplastic adrenals in suicide victims, corroborating with such hypothesis [161].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [161]
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- Authors
- Hiroi, N., Wong, M. L., Licinio, J., Park, C., Young, M., Gold, P. W., Chrousos, G. P., & Bornstein, S. R.
- Affiliations
- National Institutes of Health (US)
- University of California, Los Angeles (US)
- Corresponding author
- Bornstein, S R
- Venue
- Molecular Psychiatry
- Published
- 2001-08-29
- Volume
- 6
- Issue
- 5
- Pages
- 540-546
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2016055236
- Cited by
- 124
- References
- 38
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 3 · 2015: 4 · 2014: 11 · 2013: 9 · 2012: 6
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe
- National Institutes of Health
- Japan Society for the Promotion of Science
- National Heart, Lung, and Blood Institute (K30HL004526, K30 HL04526)
- National Institute of General Medical Sciences (U01 GM61394, U01GM061394)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK58851, R01DK058851)
- National Center for Complementary and Integrative Health (P50AT00151, P50AT000151)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- corticotropin-releasing factor, CRH receptor 1, CRH receptor 2, mRNA expression, suicide, pituitary gland, hypothalamic-pituitary-adrenal axis, stress response
- MeSH terms
- CRF Receptor, Type 1, Adolescent, Adult, Aged, Brain, Humans, Middle Aged, Organ Specificity, Pituitary Gland, Reference Values, RNA, Messenger, Suicide, Transcription, Genetic, Polymerase Chain Reaction, In Situ Hybridization, Receptors, Corticotropin-Releasing Hormone
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