Large-scale analysis of glucocorticoid target genes in rat hypothalamus
Abstract
Insufficient glucocorticoid (GC) signaling is frequently observed in major depressive disorder (MDD). Since emotional and behavioral symptoms are often accompanied by disturbances in hypothalamic systems, GC insufficiency in this region is regarded as important in the pathogenesis of MDD. In this study, 22 early GC-responsive genes comprising 15 up-regulated and 7 down-regulated genes in rat hypothalamus were identified as being regulated at least two-fold by dexamethasone using microarray with 22 599 unique transcripts. Among these 22 genes, five of which are novel GC-responsive genes, the expression patterns of sgk, bcl6, pdk4, and plekhf1 were examined in vitro in detail, and GC-responsive regions were identified only within the promoter of sgk. This suggests that glucocorticoid response element-independent pathways also play a critical role in early GC-response in hypothalamus. Considering that a number of these GC-responsive genes are candidate neuronal regulators, this gene list should be useful in clarifying the relationship between GC insufficiency and the pathogenesis of MDD.
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Cerebral SGK1 is upregulated by glucocorticoids, corticotropin releasing hormone, hyperactivity, intracranial self-stimulation, chronic escalating morphine regimen, and clozapine.
“Cerebral SGK1 is upregulated by glucocorticoids (Sato et al. 2008;Sarabdjitsingh et al. 2010), corticotropin releasing hormone (Sheng et al. 2008), hyperactivity (Kalinichev et al. 2008), intracranial self-stimulation (Huguet et al. 2009), chronic escalating morphine regimen (Befort et al. 2008) and administration of the antipsychotic drug clozapine (Robbins et al. 2008).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Sato et al. 2008
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Kunugi, H., Ida, I., Owashi, T., Kimura, M., Inoue, Y., Nakagawa, S., Yabana, T., Urushibara, T., Kanai, R., Aihara, M., et al. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300868 · Cited by 200 · see citing works
Self-citationReduced Glucocorticoid Receptor α Expression in Mood Disorder Patients and First-Degree Relatives
Matsubara, T., Funato, H., Kobayashi, A., Nobumoto, M., & Watanabe, Y. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.09.026 · Cited by 94 · cited 5× · see citing works
“Rapid neurophysiological and behavioral effects of GCs have been identified that share signaling pathways with second messengers including Ca2 + and Protein kinase C and some of these are not affected by classic antagonists of GR (RU-38486) (Falkenstein et al. 2000).”
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Stress Hormone Regulation: Biological Role and Translation into Therapy
Holsboer, F., & Ising, M. (2010) · Annual Review of Psychology · doi:10.1146/annurev.psych.093008.100321 · Cited by 473 · see citing works
Anacker, C., Cattaneo, A., Musaelyan, K., Zunszain, P. A., Horowitz, M., Molteni, R., Luoni, A., Calabrese, F., Tansey, K., Gennarelli, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300886110 · Cited by 319 · see citing works
Lee, R. S., Tamashiro, K. L. K., Yang, X., Purcell, R. H., Harvey, A., Willour, V. L., Huo, Y., Rongione, M., Wand, G. S., & Potash, J. B. (2010) · Endocrinology · doi:10.1210/en.2010-0225 · Cited by 275 · see citing works
Significance of SGK1 in the regulation of neuronal function
Lang, F., Strutz-Seebohm, N., Seebohm, G., & Lang, U. E. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.190926 · Cited by 170 · see citing works
Behavioral effects of SGK1 knockout in VTA and dopamine neurons
Doyle, M. A., Stark, A. R., Fejes-Tóth, G., Náray-Fejes-Tóth, A., & Mazei-Robison, M. S. (2020) · Scientific Reports · doi:10.1038/s41598-020-71681-9 · Cited by 9 · see citing works
- Authors
- Sato, H., Horikawa, Y., Iizuka, K., Sakurai, N., Tanaka, T., Shihara, N., Oshima, A., Takeda, J., & Mikuni, M.
- Affiliations
- Gunma University (JP)
- Japan Science and Technology Agency (JP)
- Institute for Molecular and Cellular Regulation, Gunma University (JP)
- Corresponding author
- Horikawa, Yukio
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2008-07
- Volume
- 106
- Issue
- 2
- Pages
- 805-814
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2059722505
- Cited by
- 46
- References
- 2
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 3
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- hypothalamus, major depressive disorder, glucocorticoid insufficiency, dexamethasone, SGK, BCL6, PDK4, glucocorticoid response element, gene expression profiling, rats
- MeSH terms
- Animals, Dexamethasone, Gene Expression Regulation, Glucocorticoids, HeLa Cells, Humans, Hypothalamus, Male, Transfection, Signal Transduction, Rats, Sprague-Dawley, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Rats
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