Steroid hormone receptor expression and function in microglia
Open accessAbstract
Steroid hormones such as glucocorticoids and estrogens are well‐known regulators of peripheral immune responses and also show anti‐inflammatory properties in the brain. However, the expression of steroid hormone receptors in microglia, the pivotal immune cell that coordinates the brain inflammatory response, is still controversial. Here we use real time RT‐PCR to show that microglia, isolated from adult fms ‐EGFP mice by FACS, express glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and estrogen receptor alpha (ERα). GR was the most abundant steroid hormone receptor transcript in microglia. The presence of GR and ERα immunoreactivity was further confirmed in vivo at the ultrastructural level. To understand the role of steroid hormone receptors during the inflammation process, we evaluated the expression of steroid hormone receptors after inflammatory challenge and found a significant down‐regulation of GR, MR, and ERα in microglia. Finally, we tested the immunomodulatory properties of estrogens and glucocorticoids. Estradiol benzoate did not have any significant impact on the inflammatory profile of ex vivo sorted microglia, either in resting conditions or after challenge. Furthermore, corticosterone was a more consistent anti‐inflammatory agent than 17β‐estradiol in vitro . Our results support the hypothesis that adult microglia are a direct target of steroid hormones and that glucocorticoids, through the predominant expression of GR and MR, are the primary steroid hormone regulators of microglial inflammatory activity. The down‐regulation of steroid hormone receptors after LPS challenge may serve as a prerequisite to suppressing the anti‐inflammatory actions of endogenous steroid hormones on the immune system, and contribute to a sustained activation of microglia. © 2008 Wiley‐Liss, Inc.
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Microglial cells are prime targets of glucocorticoids in the CNS owing to predominant glucocorticoid receptor expression, and through them glucocorticoids perform major regulatory functions on CNS innate immunity in health and disease.
“Microglial cells represent prime targets of GCs in the CNS owing to a predominant expression of GR (65). Through these key innate immune cells, GCs therefore perform major regulatory functions on the innate immune system of the CNS in health and disease.”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [65]
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G protein-coupled estrogen receptor in immune cells and its role in immune-related diseases
Notas, G., Kampa, M., & Castanas, E. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.579420 · Cited by 109 · see citing works
Sahasrabuddhe, V., & Ghosh, H. S. (2022) · Cell Reports · doi:10.1016/j.celrep.2021.110252 · Cited by 91 · see citing works
Less can be more: Fine tuning the maternal brain
Pawluski, J. L., Hoekzema, E., Leuner, B., & Lonstein, J. S. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.11.045 · Cited by 91 · see citing works
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Greater glucocorticoid receptor activation in hippocampus of aged rats sensitizes microglia
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Glucocorticoid signaling in myeloid cells worsens acute CNS injury and inflammation
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Microglia express functional 11β‐hydroxysteroid dehydrogenase type 1
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Self-citationConstitutive expression of CX3CR1-BAC-Cre introduces minimal off-target effects in microglia
Mroue-Ruiz, F. H., Desai, B., Garvin, M. M., Shehu, J. H., Kamau, F., Kar, U., & Bolton, J. L. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.153657 · Cited by 3 · see citing works
- Authors
- Sierra, A., Gottfried‐Blackmore, A., Milner, T. A., McEwen, B. S., & Bulloch, K.
- Affiliations
- Rockefeller University (US)
- Weill Cornell Medicine (US)
- Corresponding author
- Bulloch, Karen
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2008-02-19
- Volume
- 56
- Issue
- 6
- Pages
- 659-674
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2042197302
- Cited by
- 405
- References
- 77
- Citations by year
- 2026: 17 · 2025: 22 · 2024: 27 · 2023: 17 · 2022: 21 · 2021: 40 · 2020: 32 · 2019: 34 · 2018: 30 · 2017: 16 · 2016: 26 · 2015: 12 · 2014: 13 · 2013: 20 · 2012: 15
- FWCI
- 13.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cold Spring Harbor Laboratory
- National Institutes of Health (AG16765, HL18974)
- National Institute on Aging (AG-16765, P01AG016765)
- National Heart, Lung, and Blood Institute (HL-18974, P01HL018974)
- National Institute on Drug Abuse (R01DA008259, DA08259)
- National Institute of Neurological Disorders and Stroke (NS007080, R01NS007080)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- microglia, steroid hormone receptors, glucocorticoid receptor, mineralocorticoid receptor, estrogen receptor alpha, glucocorticoids, estrogen, corticosterone, estradiol benzoate, lipopolysaccharide challenge, neuroinflammation, anti-inflammatory activity, microglial activation
- MeSH terms
- Animals, Cells, Cultured, Dose-Response Relationship, Drug, Estradiol, Estrogens, Female, Flow Cytometry, Male, Mice, Inbred C57BL, Mice, Transgenic, Ovariectomy, Receptors, Steroid, Sex Characteristics, Time Factors, Down-Regulation, Gene Expression, Cytokines, Microscopy, Immunoelectron, Microglia, Green Fluorescent Proteins, Mice
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