Hypothalamic–pituitary–adrenal axis dysregulation and behavioral analysis of mouse mutants with altered glucocorticoid or mineralocorticoid receptor function: Review
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Corticosteroid receptors are critical for the maintenance of homeostasis after both psychological and physiological stress. To understand the different roles and interactions of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) during stress, it is necessary to dissect the role of corticosteroid signaling at both the system and sub-system level. A variety of GR transgenic mouse lines have recently been used to characterize the role of GR in the CNS as a whole and particularly in the forebrain. We will describe both the behavioral and cellular/molecular implications of disrupting GR function in these animal models and describe the implications of this data for our understanding of normal endocrine function and stress adaptation. MRs in tight epithelia have a long established role in sodium homeostasis. Recently however, evidence has suggested that MRs in the limbic brain also play an important role in psychological stress. Just as with GR, targeted mutations in MR induce a variety of behavioral changes associated with stress adaptation. In this review, we will discuss the implications of this work on MR. Finally, we will discuss the possible interaction between MR and GR and how future work using double mutants (through conventional means or virus based gene alteration) will be needed to more fully understand how signaling through these two steroid receptors provides the adaptive mechanisms to deal with a variety of stressors.
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Glucocorticoid receptors are ubiquitously expressed in the brain but most abundant in the PVN and hippocampus; mineralocorticoid receptor expression is mostly confined to limbic sites regulating salt appetite and autonomic outflow.
“Although GRs are ubiquitously expressed in the brain, they are most abundant in the PVN and the hippocampus. In contrast, MR expression appears mostly confined to a few limbic sites regulating salt appetite and autonomic outflow (70, 71).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [71]
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- Authors
- Kolber, B. J., Wieczorek, L., & Muglia, L. J.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Muglia, Louis J.
- Venue
- Stress
- Publisher
- Informa UK Limited
- Published
- 2008-01
- Volume
- 11
- Issue
- 5
- Pages
- 321-338
- ISSN
- 1025-3890 (ISSN-L)
- 1607-8888
- PMC
- PMC2744095
- OpenAlex
- W2135772988
- Cited by
- 106
- References
- 79
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 13 · 2019: 7 · 2018: 6 · 2017: 11 · 2016: 4 · 2015: 3 · 2014: 10 · 2013: 5 · 2012: 12
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stress (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG018876)
- National Institute of Mental Health (F31MH075250, F31MH084391)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- hypothalamic-pituitary-adrenal axis, glucocorticoid receptor, mineralocorticoid receptor, corticosteroid signaling, stress adaptation, mouse mutants, limbic system, sodium homeostasis, forebrain, endocrine function
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Circadian Rhythm, Hypothalamo-Hypophyseal System, Learning Disabilities, Memory Disorders, Mice, Mutant Strains, Mice, Transgenic, Pituitary-Adrenal System, Receptors, Glucocorticoid, Stress, Psychological, Prosencephalon, Receptors, Mineralocorticoid, Mice, Knockout, Mice
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