Disrupted corticosterone pulsatile patterns attenuate responsiveness to glucocorticoid signaling in rat brain
Abstract
Chronically elevated circulating glucocorticoid levels are although to enhance vulnerability to psychopathology. Here we hypothesized that such sustained glucocorticoid levels, disturbing corticosterone pulsatility, attenuate glucocorticoid receptor signaling and target gene responsiveness to an acute challenge in the rat brain. Rats were implanted with vehicle or 40 or 100% corticosterone pellets known to flatten ultradian and circadian rhythmicity while maintaining daily average levels or mimic pathological conditions. Additionally, recovery from constant exposure was studied in groups that had the pellet removed 24 h prior to the challenge. Molecular markers for receptor responsiveness (receptor levels, nuclear translocation, promoter occupancy, and target gene expression) to an acute challenge mimicking the stress response (3 mg/kg ip) were studied in the hippocampal area. Implantation of 40 and 100% corticosterone pellets dose-dependently down-regulated glucocorticoid receptor and attenuated mineralocorticoid receptor and glucocorticoid receptor translocation to the acute challenge. Interestingly, whereas target gene Gilz expression to the challenge was already attenuated by tonic daily average levels (40%), Sgk-1 was affected only after constant high corticosterone exposure (100%), indicating altered receptor responsiveness due to treatment. Washout of 100% corticosterone recovered all molecular markers (partial), whereas removal of the 40% corticosterone pellet still a…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 Sarabdjitsingh et al. 2010
Cites
Chronic stress: Implications for neuronal morphology, function and neurogenesis
Joëls, M., Karst, H., Krugers, H. J., & Lucassen, P. J. (2007) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.04.001 · Cited by 381 · see citing works
Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription
Stavreva, D. A., Wiench, M., John, S., Conway-Campbell, B. L., McKenna, M. A., Pooley, J. R., Johnson, T. A., Voss, T. C., Lightman, S. L., & Hager, G. L. (2009) · Nature Cell Biology · doi:10.1038/ncb1922 · Cited by 375 · see citing works
Cortisol pulsatility and its role in stress regulation and health
YOUNG, E., ABELSON, J., & LIGHTMAN, S. (2004) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2004.07.001 · Cited by 355 · see citing works
Droste, S. K., de Groote, L., Atkinson, H. C., Lightman, S. L., Reul, J. M. H. M., & Linthorst, A. C. E. (2008) · Endocrinology · doi:10.1210/en.2008-0103 · Cited by 280 · see citing works
Windle, R. J., Wood, S. A., Lightman, S. L., & Ingram, C. D. (1998) · Endocrinology · doi:10.1210/endo.139.10.6238 · Cited by 201 · see citing works
Meijer, O. C., Steenbergen, P. J., & de Kloet, E. R. (2000) · Endocrinology · doi:10.1210/endo.141.6.7489 · Cited by 200 · see citing works
Self-citationConway-Campbell, B. L., McKenna, M. A., Wiles, C. C., Atkinson, H. C., de Kloet, E. R., & Lightman, S. L. (2007) · Endocrinology · doi:10.1210/en.2007-0585 · Cited by 125 · see citing works
van der Laan, S., Lachize, S. B., Schouten, T. G., Vreugdenhil, E., de Kloet, E. R., & Meijer, O. C. (2005) · Brain Research · doi:10.1016/j.brainres.2005.08.011 · Cited by 27 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Joëls, M., Sarabdjitsingh, R. A., & Karst, H. (2012) · Pharmacological Reviews · doi:10.1124/pr.112.005892 · Cited by 425 · see citing works
Self-citationThe crucial role of pulsatile activity of the HPA axis for continuous dynamic equilibration
Lightman, S. L., & Conway-Campbell, B. L. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2914 · Cited by 390 · see citing works
Spiga, F., Walker, J. J., Terry, J. R., & Lightman, S. (2014) · Comprehensive Physiology · doi:10.1002/j.2040-4603.2014.tb00576.x · Cited by 272 · see citing works
“Consistent with these data, disruption of the ultradian pattern of corticosterone secretion results in changes in GR receptor sensitivity with profound effects on the glucocorticoid responsiveness of target tissues (166).”
Spiga, F., Walker, J. J., Terry, J. R., & Lightman, S. L. (2014) · Comprehensive Physiology · doi:10.1002/cphy.c140003 · Cited by 267 · see citing works
de Kloet, E. R., Meijer, O. C., Nicola, A. F. D., Rijk, R. H. D., & Joëls, M. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.02.003 · Cited by 279 · see citing works
“In contrast, irGR nuclear translocation reflects the ultradian rhythm (Sarabdjitsingh et al., 2009; Sarabdjitsingh et al., 2010) and imposes cyclic gene expression patterns (Conway-Campbell et al., 2010).”
Self-citationStratified medicine for mental disorders
Schumann, G., Binder, E. B., Holte, A., de Kloet, E. R., Oedegaard, K. J., Robbins, T. W., Walker-Tilley, T. R., Bitter, I., Brown, V. J., Buitelaar, J., et al. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.09.010 · Cited by 186 · see citing works
“Also the ultradian and circadian rhythms provide a basis for the threshold and sensitivity of the stress system: the magnitude and nature of the behavioural and physiological stress response varies depending on the phase of the hourly cortisol pulse (Sarabdjitsingh et al. 2010).”
BackgroundFrodl, T., Carballedo, A., Hughes, M. M., Saleh, K., Fagan, A., Skokauskas, N., McLoughlin, D. M., Meaney, J., O'Keane, V, & Connor, T. J. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.14 · Cited by 176 · see citing works
“In this context, the glucocorticoid-inducible genes Leucin Zipper (GILZ) and serum and glucocorticoid-inducible kinase-1 (SGK-1) are target genes activated by GR activation, and their expression has been shown to be disrupted in the hippocampus as a result of hypercortisolemia.(20) In addition, a recent study demonstr…”
From Receptor Balance to Rational Glucocorticoid Therapy
de Kloet, E. R. (2014) · Endocrinology · doi:10.1210/en.2014-1048 · Cited by 205 · see citing works
“nucleus over the interpulse interval (54).”
BackgroundSignificance 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
“Putative role of SGK1 in neuronal function 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…”
BackgroundOdermatt, A., & Kratschmar, D. V. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.07.020 · Cited by 155 · see citing works
Herman, J. P., Nawreen, N., Smail, M. A., & Cotella, E. M. (2020) · Stress · doi:10.1080/10253890.2020.1859475 · Cited by 180 · see citing works
“Pulsatile release is critical for appropriate glucocorticoid signaling, as blocking pulsatile release by constant delivery of glucocorticoids impairs GR nuclear translocation and thereby modifies glucocorticoid actions on transcription (Russell et al., 2015; Sarabdjitsingh et al., 2010).”
BackgroundConway‐Campbell, B. L., Sarabdjitsingh, R. A., McKenna, M. A., Pooley, J. R., Kershaw, Y. M., Meijer, O. C., De Kloet, E. R., & Lightman, S. L. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02051.x · Cited by 137 · see citing works
Self-citationHPA-axis and inflammatory reactivity to acute stress is related with basal HPA-axis activity
Chen, X., Gianferante, D., Hanlin, L. C., Fiksdal, A. S., Breines, J. G., Thoma, M. V., & Rohleder, N. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.01.035 · Cited by 144 · see citing works
“…cortisol decline, on the other hand, can be conceptualized as an demonstration of negative feedback in HPA axis (Lightman and Conway-Campbell, 2010; Sarabdjitsingh et al., 2010) and reduced glucocorticoid sensitivity was found to be associated with flatter diurnal declines in females with major…”
BackgroundThe cortisol switch between vulnerability and resilience
de Kloet, E. R., & Joëls, M. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01934-8 · Cited by 153 · see citing works
“This hourly gene pulsing is a prerequisite for the maintenance of tissue responsivity to CORT [37, 38].”
Sarabdjitsingh, R. A., Conway-Campbell, B. L., Leggett, J. D., Waite, E. J., Meijer, O. C., de Kloet, E. R., & Lightman, S. L. (2010) · Endocrinology · doi:10.1210/en.2010-0832 · Cited by 116 · see citing works
Self-citationSchrepf, A., O’Donnell, M. A., Luo, Y., Bradley, C. S., Kreder, K. J., & Lutgendorf, S. K. (2014) · Pain · doi:10.1016/j.pain.2014.05.029 · Cited by 105 · see citing works
Two Populations of Glucocorticoid Receptor-Binding Sites in the Male Rat Hippocampal Genome
Polman, J. A. E., de Kloet, E. R., & Datson, N. A. (2013) · Endocrinology · doi:10.1210/en.2012-2187 · Cited by 95 · see citing works
“Details of all the validated GBS are present in Supplemental Table 3 (GBS number): Nrxn1 (1826), Ndnl2 (1529), St3gal3 (529), Lyst (535), Slc7a6 (640), Arpc2 (759), Cacna2d3 (1540), Serp2 (61), MT2a (63), Per1_2 (1362), Ddit4 (211), Klf9 (25), Per1_1 (12).”
BackgroundSelf-citationPolman, J. A. E., Hunter, R. G., Speksnijder, N., van den Oever, J. M. E., Korobko, O. B., McEwen, B. S., de Kloet, E. R., & Datson, N. A. (2012) · Endocrinology · doi:10.1210/en.2012-1255 · Cited by 100 · see citing works
Self-citationTop‐down and bottom‐up control of stress‐coping
de Kloet, E. R., de Kloet, S. F., de Kloet, C. S., & de Kloet, A. D. (2018) · Journal of Neuroendocrinology · doi:10.1111/jne.12675 · Cited by 120 · see citing works
Ultradian corticosterone pulses balance glutamatergic transmission and synaptic plasticity
Sarabdjitsingh, R. A., Jézéquel, J., Pasricha, N., Mikasová, L., Kerkhofs, A., Karst, H., Groc, L., & Joëls, M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411216111 · Cited by 80 · see citing works
Self-citationHall, B. S., Moda, R. N., & Liston, C. M. (2014) · Neurobiology of Stress · doi:10.1016/j.ynstr.2014.10.008 · Cited by 90 · see citing works
“Conversely, in chronic stress models, disruptions of the ultradian oscillation alter gene expression responses in these regions and cause correlated changes in locomotor activity and risk assessment behaviors (Sarabdjitsingh et al., 2010a,b).”
BackgroundPandey, G. N., Rizavi, H. S., Ren, X., Dwivedi, Y., & Palkovits, M. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.06.020 · Cited by 71 · see citing works
“GILZ is a target gene activated by GR activation and its expression is shown to be disrupted in the hippocampus as a result of hypercortisolemia in the rat (Sarabdjitsingh et al., 2010).”
BackgroundSchouten, M., Bielefeld, P., García‐Corzo, L., Passchier, E. M. J., Gradari, S., Jungenitz, T., Pons‐Espinal, M., Gebara, E., Martín‐Suárez, S., Lucassen, P. J., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0440-2 · Cited by 75 · see citing works
Specific regulatory motifs predict glucocorticoid responsiveness of hippocampal gene expression.
Datson, N., Polman, J., de Jonge, R. T., van Boheemen, P. T. M., van Maanen, E., Welten, J., McEwen, B., Meiland, H. C., & Meijer, O. (2011) · Endocrinology · doi:10.1210/en.2011-0287 · Cited by 73 · see citing works
“ChIP to study binding of GR to predicted GREs was performed as published (14).”
MethodSelf-citationFitzsimons, C., Herbert, J., Schouten, M., Meijer, O., Lucassen, P., & Lightman, S. (2016) · Frontiers in neuroendocrinology (Print) · doi:10.1016/j.yfrne.2016.05.001 · Cited by 68 · see citing works
“This mechanism seems to be relevant for several tissues, including the brain, where the interruption of GC rhythmicity attenuates gene expression responsiveness to (changes in) GC signaling (Sarabdjitsingh et al., 2010b).”
Self-citationMolecular dynamics of ultradian glucocorticoid receptor action
Conway-Campbell, B. L., Pooley, J. R., Hager, G. L., & Lightman, S. L. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.08.014 · Cited by 68 · see citing works
Glucocorticoid pulsatility and rapid corticosteroid actions in the central stress response
Sarabdjitsingh, R. A., Joëls, M., & de Kloet, E. R. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.09.017 · Cited by 48 · see citing works
“Data adapted from [63].”
BackgroundInfluentialSelf-citationCarter, B. S., Hamilton, D. E., & Thompson, R. C. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00139 · Cited by 56 · see citing works
“A subset of measured mRNAs have been reported to be regulated in the brain in vivo by glucocorticoids or stress conditions [e.g., Fkbp5 (Scharf et al., 2011), Gfap (O’Callaghan et al., 1989), Glul (Patel et al., 1983), Sgk1 (Sarabdjitsingh et al., 2010)], but a number of astrocyteenriched mRNAs demonstrate novel in vi…”
BackgroundInfluentialGil‐Lozano, M., Wu, W. K., Martchenko, A., & Brubaker, P. L. (2015) · Endocrinology · doi:10.1210/en.2015-1732 · Cited by 61 · see citing works
“This procedure maintains constant corticosterone levels within the physiological range (24) and was used to determine whether glucocorticoids play a role as an entrainment factor for the rhythmic activity of the L-cell.”
MethodRobertson, S., Rohwer, J. M., Hapgood, J. P., & Louw, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064831 · Cited by 55 · see citing works
Dattilo, V., Amato, R., Perrotti, N., & Gennarelli, M. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00826 · Cited by 49 · see citing works
“The brain expression of SGK1 is positively regulated by glucocorticoids (Sato et al., 2008; Sarabdjitsingh et al., 2010), motor hyperstimulation (Kalinichev et al.”
BackgroundLi, Z.-Y., Jiang, Y., Liu, Y.-M., Guo, Z., Shen, S.-N., Liu, X., & Pan, R. (2014) · Progress in Neuro-psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.02.010 · Cited by 49
Cell type specificity of glucocorticoid signaling in the adult mouse hippocampus
Viho, E. M. G., Buurstede, J. C., Berkhout, J. B., Mahfouz, A. E., & Meijer, O. C. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.13072 · Cited by 46 · see citing works
Self-citationSarabdjitsingh, R. A., Meijer, O. C., & de Kloet, E. R. (2010) · Brain Research · doi:10.1016/j.brainres.2010.03.052 · Cited by 40 · see citing works
“For example, complete redistribution of nuclear GR over the cytoplasm after steroid withdrawalmay last more than 24 h (Hache et al., 1999), while in vivo GR is rapidly shuttled in and out of the nucleus on an hourly time-scale (Conway-Campbell et al., 2007; Sarabdjitsingh et al., 2010).”
Self-citationBonapersona, V., Damsteegt, R., Adams, M. L., van Weert, L. T. C. M., Meijer, O. C., Joëls, M., & Sarabdjitsingh, R. A. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00181 · Cited by 29 · see citing works
“This results in an increased refractory time in which the animals are in a non-responsive state, giving rise to apparent stress hyporesponsiveness (Windle et al., 2008; Lightman and Conway-Campbell, 2010; Sarabdjitsingh et al., 2010).”
BackgroundMethodInfluentialSelf-citationHinds, L. R., Chun, L. E., Woodruff, E. R., Christensen, J. A., Hartsock, M. J., & Spencer, R. L. (2017) · PLOS ONE · doi:10.1371/journal.pone.0175075 · Cited by 40 · see citing works
Sarabdjitsingh, R. A., Zhou, M., Yau, J. L. W., Webster, S. P., Walker, B. R., Seckl, J. R., Joëls, M., & Krugers, H. J. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.01.042 · Cited by 31 · see citing works
Self-citationBarr, J. L., & Forster, G. L. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.03.020 · Cited by 39 · see citing works
“However, GR expression is more sensitive to corticosterone-induced down-regulation (Sarabdjitsingh et al., 2010).”
BackgroundDanan, D., Matar, M. A., Kaplan, Z., Zohar, J., & Cohen, H. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.09.023 · Cited by 35 · see citing works
“In the rat, corticosterone pulses have a near-hourly frequency (Sarabdjitsingh et al., 2010a), and changes in the amplitude of these pulses throughout the 24 h cycle determine the circadian variation in hormone secretion (Spiga et al., 2015).”
BackgroundShyti, R., Eikermann‐Haerter, K., van Heiningen, S. H., Meijer, O. C., Ayata, C., Joëls, M., Ferrari, M. D., van den Maagdenberg, A. M. J. M., & Tolner, E. A. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.10.015 · Cited by 35 · see citing works
“Corticosterone plasma levels were determined by a commercial radioactive immunoassay (MP Biomedicals Inc., Costa Mesa, CA) according to manufacturer's instructions (Sarabdjitsingh et al., 2010).”
Self-citationHippocampal Fast Glutamatergic Transmission Is Transiently Regulated by Corticosterone Pulsatility
Sarabdjitsingh, R. A., Pasricha, N., Smeets, J. A. S., Kerkhofs, A., Mikasová, L., Karst, H., Groc, L., & Joëls, M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0145858 · Cited by 35 · see citing works
Self-citationSarabdjitsingh, R. A., Spiga, F., Oitzl, M. S., Kershaw, Y., Meijer, O. C., Lightman, S. L., & De Kloet, E. R. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02004.x · Cited by 35 · see citing works
Self-citationRonchi, C. L., Sbiera, S., Leich, E., Tissier, F., Steinhauer, S., Deutschbein, T., Faßnacht, M., & Allolio, B. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2669 · Cited by 41 · see citing works
“hibit SGK1 expression through a down-regulation of GC receptors in brain (35).”
Ayyar, V. S., Almon, R. R., Jusko, W. J., & DuBois, D. C. (2015) · Physiological Reports · doi:10.14814/phy2.12382 · Cited by 32 · see citing works
Lee, M.-S., Kim, Y., Park, W.-S., Park, O. K., Kwon, S.-H., Hong, K. S., Rhim, H., Shim, I., Morita, K., Wong, D. L., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.137 · Cited by 29 · see citing works
The activity of the glucocorticoid receptor is regulated by SUMO conjugation to FKBP51
Antunica-Noguerol, M., Budziñski, M. L., Druker, J., Gassen, N. C., Sokn, C., Senin, S. A., Aprile-Garcia, F., Holsboer, F., Rein, T., Liberman, A. C., et al. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.44 · Cited by 29 · see citing works
“upregulated byGCs in the hippocampus.(33,34) In linewith these”
BackgroundGeorge, C. L., Birnie, M. T., Flynn, B. P., Kershaw, Y. M., Lightman, S. L., & Conway-Campbell, B. L. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.10.019 · Cited by 30 · see citing works
“Sgk1 is a widely expressed kinase that is regulated by glucocorticoids via a regulatory DNA element approximately 1 kb upstream of the transcriptional start site (TSS) (Webster et al., 1993a; Maiyar et al., 1997; Sato et al., 2008).”
BackgroundGil‐Lozano, M., Romaní‐Pérez, M., Outeiriño‐Iglesias, V., Vigo, E., Brubaker, P. L., González-Matías, L. C., & Mallo, F. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00529.2012 · Cited by 29 · see citing works
“Interestingly, it has been previously suggested that disruption of the corticosterone rhythm and maintenance of constant glucocorticoid levels, as described in the present study, may result in loss of adrenal gland sensitivity and attenuation of HPA axis responsiveness (1, 39, 55).”
BackgroundDanan, D., Todder, D., Zohar, J., & Cohen, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116050 · Cited by 26 · see citing works
Cardio‐metabolic consequences of glucocorticoid replacement: relevance of ultradian signalling
Henley, D., & Lightman, S. L. (2014) · Clinical Endocrinology · doi:10.1111/cen.12422 · Cited by 22 · see citing works
den Boon, F. S., & Sarabdjitsingh, R. A. (2017) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2017.09.001 · Cited by 27 · see citing works
Self-citationGlucocorticoids are active players and therapeutic targets in atherosclerotic cardiovascular disease
van der Sluis, R. J., & Hoekstra, M. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.110728 · Cited by 27 · see citing works
“Importantly, preclinical studies by Sarabdjitsingh et al. (2010) have observed a significant flattening of the plasma glucocorticoid rhythmicity upon chronic glucocorticoid receptor overactivation in rats.”
Srinivasan, M., & Walker, C. L. (2022) · ASN NEURO · doi:10.1177/17590914221120190 · Cited by 25 · see citing works
“Acute corticosterone exposure continued to decrease GILZ transcript in conditions of average circulating cortisol and had no effects in hypercortisolemia(Sarabdjitsingh et al., 2010).”
BackgroundMR/GR Signaling in the Brain during the Stress Response
de Kloet, E. R., & Meijer, O. C. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.87234 · Cited by 19 · see citing works
Self-citationFrodl, T., Carballedo, A., Frey, E.-M., O'Keane, V., Skokauskas, N., Morris, D., Gill, M., Hughes, M. M., Harkin, A., & Connor, T. (2014) · Development and Psychopathology · doi:10.1017/s0954579414000972 · Cited by 20 · see citing works
“…inducible leucin zipper (GILZ), serum and glucocorticoid-inducible kinase-1 (SGK1), and FK506 binding protein 5 (FKBP5), are target genes activated by GR activation; their expression has been shown to be disrupted in the hippocampus as a result of hypercortisolemia (Sarabdjitsingh et al., 2010).”
BackgroundJoëls, M., Karst, H., & Tasker, J. G. (2024) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2024.101146 · Cited by 23 · see citing works
“…course of > 1 hr has been studied mainly in the context of the stress response, although ultradian CORT peaks causing pulsatile genomic actions via GR were also investigated and found to be important to keep neuronal systems responsive (Sarabdjitsingh et al., 2010b; Sarabdjitsingh et al., 2010a).”
BackgroundHuzard, D., Rappeneau, V., Meijer, O. C., Touma, C., Arango-Lievano, M., Garabedian, M. J., & Jeanneteau, F. D. (2020) · Stress · doi:10.1080/10253890.2020.1806226 · Cited by 23 · see citing works
“The precision of glucocorticoid action also varies across neuronal networks if the context of stress occurs during the ascending or descending phases of the ultradian glucocorticoid oscillations (Sarabdjitsingh et al., 2010a, 2010b, 2010c).”
BackgroundSelf-citationSpeksnijder, N., Christensen, K. V., Didriksen, M., de Kloet, E. R., & Datson, N. A. (2012) · Journal of Molecular Neuroscience · doi:10.1007/s12031-012-9809-2 · Cited by 16 · see citing works
“Chromatin Immunoprecipitation The exact procedure is described in Sarabdjitsingh et al. (2010a).”
Self-citationA proposed role for glucocorticoids in mediating dopamine-dependent cue-reward learning
Lopez, S. A., & Flagel, S. B. (2020) · Stress · doi:10.1080/10253890.2020.1768240 · Cited by 14 · see citing works
“…in humans and corticosterone in rodents—circulate both peripherally and centrally in fluctuating concentrations that follow an ultra-radian and circadian rhythm (Kalsbeek et al., 2012; Lightman & Conway-Campbell, 2010; Qian et al., 2012; Sarabdjitsingh et al., 2010; Spiga et al., 2014).”
Backgrounddel Burgo, L. S., Cortés, R., Mengod, G., Montaña, M., del Caño, G. G., & Sallés, J. (2012) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.04.007 · Cited by 13 · see citing works
“The lack of GR mRNA downregulation at the hippocampus is at odds with the aforementioned studies (Sapolsky and McEwen, 1985; Sarabdjitsingh et al., 2010), but agrees with previous studies that used comparable corticosterone pellets in adrenally intact rats (Akana et al., 1992; Herman and Spencer,…”
Coping with the multifaceted and multifunctional role of cortisol in the brain
de Kloet, E. R. (2024) · Neuroscience Applied · doi:10.1016/j.nsa.2024.104047 · Cited by 14 · see citing works
“GR binding to CORT has a lower affinity and shows nuclear translocation in parallel with changing CORT concentrations during the ultradian rhythm and after stress (Sarabdjitsingh et al., 2010), (Conway-Campbell et al., 2010).”
Yoshimura, M., Flynn, B. P., Kershaw, Y. M., Zhao, Z., Ueta, Y., Lightman, S. L., & Conway-Campbell, B. L. (2023) · Communications Biology · doi:10.1038/s42003-023-05347-3 · Cited by 16 · see citing works
“…studies have demonstrated that pulsatile activation is necessary to maintain optimal transcriptional activity of glucocorticoid receptors (GRs) in cell lines, and rat liver and brain 5 – 8 , as well as HPA axis sensitivity, neuronal activation and behavioural responses to stress in rats 9 .”
Glucocorticoid feedback paradox: a homage to Mary Dallman
de Kloet, E. R. (2023) · Stress · doi:10.1080/10253890.2023.2247090 · Cited by 11 · see citing works
“Furthermore, GR resistance develops if replacement with corticosterone is not pulsatile, but continuous, as is the case with the steady release of the steroid from a subcutaneously (sc)-implanted corticosterone pellet (den Boon & Sarabdjitsingh, 2017; Sarabdjitsingh et al., 2010).”
BackgroundBielefeld, P., Schouten, M., Lucassen, P. J., & Fitzsimons, C. P. (2017) · Neurogenesis · doi:10.1080/23262133.2016.1262934 · Cited by 11 · see citing works
The importance of the circadian trough in glucocorticoid signaling: a variation on B-flat
Meijer, O., Kooijman, S., Kroon, J., & Winter, E. M. (2023) · Stress · doi:10.1080/10253890.2023.2275210 · Cited by 10 · see citing works
“…receptor expression in the brain, adiposity and thermogenic activity, and osteoporosis (Akana et al., 1992; Kroon et al., 2021; Meijer et al., 1997; Sarabdjitsingh et al., 2010; Schilperoort et al., 2021; tholen et al., 2022). likely there are many other organ systems and processes that are…”
BackgroundSelf-citationThree percent annually on systemic glucocorticoids: facts, worries and perspectives.
Meijer, O., & Pereira, A. (2019) · European Journal of Endocrinology · doi:10.1530/eje-19-0555 · Cited by 10
Self-citationIndomethacin induced gene regulation in the rat hippocampus
Sathyanesan, M., Girgenti, M. J., Warner‐Schmidt, J. L., & Newton, S. S. (2015) · Molecular Brain · doi:10.1186/s13041-015-0150-x · Cited by 9 · see citing works
“(SGK) is induced in the brain primarily by glucocorticoids [18], but also by several different stimuli and stressors, including fear conditioning, enriched environment, plus maze exposure, cell volume and drugs of abuse [19].”
BackgroundKohut, S. J., DeCicco-Skinner, K. L., Johari, S., Hurwitz, Z. E., Baumann, M. H., & Riley, A. L. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.03.012 · Cited by 8 · see citing works
Glucocorticoid therapy is a risk factor for cardiovascular diseases
Dzherieva, I. S., Волкова, Н. И., Davidenko, I. Y., Reshetnikov, I., Brovkina, S. S., Avakova, S. M., & Tishchenko, Y. V. (2022) · Medical Herald of the South of Russia · doi:10.21886/2219-8075-2022-13-3-93-106 · Cited by 8 · see citing works
Stress Research: Past, Present, and Future
de Kloet, E. R., & Joëls, M. (2012) · Springer eBooks · doi:10.1007/978-1-4614-1997-6_72 · Cited by 6 · see citing works
Brain Mineralocorticoid Receptors and Resilience to Stress.
Kanatsou, S., Joëls, M., & Krugers, H. (2019) · Vitamins and hormones · doi:10.1016/bs.vh.2018.11.001 · Cited by 7 · see citing works
Bläuer, M., Sand, J., & Laukkarinen, J. (2021) · Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · doi:10.1016/j.pan.2020.12.024 · Cited by 6 · see citing works
Corticosteroid Receptor Involvement in the Stress Response
de Kloet, E. R., DeRijk, R. H., & Meijer, O. C. (2011) · Wiley eBooks · doi:10.1002/9781118083222.ch3 · Cited by 6 · see citing works
Self-citationRapid and Slow Effects of Corticosteroid Hormones on Hippocampal Activity
Joëls, M., Sarabdjitsingh, R. A., den Boon, F. S., & Karst, H. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-802175-0.00033-4 · Cited by 5 · see citing works
Self-citationWu, A., Yang, G., Liu, G., & Zhang, J. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07542-y · Cited by 4 · see citing works
“F Schematic summary of hypercortisolism-induced neuronal apoptosis synchronized with SGK1-induced neuronal protection in GFAP + neurons in the FrA of mice after SCT.”
Giannos, P., Prokopidis, K., Forbes, S. C., Celoch, K., Candow, D. G., & Tartar, J. L. (2022) · Brain Sciences · doi:10.3390/brainsci12070825 · Cited by 3 · see citing works
“Chronically elevated circulating glucocorticoid levels may alter brain SGK1 expression in rat models, downregulating glucocorticoid receptor responsiveness [42], impairing neuronal plasticity [43], and oligodendro-”
BackgroundDifferential regulation of type 2 immunity by glucocorticoids
Song, H., & Lim, J. (2025) · BMB Reports · doi:10.5483/bmbrep.2025-0066 · Cited by 2
“Moreover, in vitro studies often use constant, high-dose exposure regimens (sub-micromolar to micromolar), contrasting with the pulsatile release of endogenous GCs, which maintain circulating concentrations in the range of 100-500 nM (92).”
Do Corticosteroid Receptor mRNA Levels Predict the Expression of Their Target Genes?
Koorneef, L. L., Viho, E. M. G., Wahl, L. F., & Meijer, O. C. (2022) · Journal of the Endocrine Society · doi:10.1210/jendso/bvac188 · Cited by 3 · see citing works
Self-citationGlucocorticoid Regulation of Neurocognitive and Neuropsychiatric Function
Pereira, A. M., & Meijer, O. C. (2016) · Springer eBooks · doi:10.1007/978-3-319-45950-9_2 · Cited by 1 · see citing works
Self-citationSarafoglou, K., Addo, O., Hodges, J. S., Brundage, R., Lightman, S., Hindmarsh, P., & Miller, B. (2022) · Hormone Research in Paediatrics · doi:10.1159/000525990 · Cited by 1
Genomic Aspects of Corticosteroid Action in the Brain
van Weert, L. T. C. M., & Meijer, O. C. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00051-1 · Cited by 1 · see citing works
Self-citationStress and Glucocorticoid Action in the Brain and Ear: Implications for Tinnitus
de Kloet, E. R., & Szczepek, A. J. (2017) · Springer eBooks · doi:10.1007/978-3-319-58397-6_2 · Cited by 3 · see citing works
Regulation of the Mineralocorticoid Receptor in Physiology and Disease
Young, M. J., Fuller, P. J., Meijer, O. C., Cole, T. J., Kanki, M., Yang, J., Ho, Q. V., Karthigan, N., & Heanue, S. (2026) · Pharmacological Reviews · doi:10.1016/j.pharmr.2026.100156
Self-citationA Hierarchical Model of the Hypothalamo-Adreno-Pituitary systemPreprint
Rota, C. L., Vuza, D. T., & Climescu-Haulica, A. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/837724
“There is also evidence of GR nuclear translocation desensitization in response to long-term constant CORT concentrations (7 days) [143]; this mechanism might underlie a ratesensitive regulation of genomic responses at ultradian time-scales, but there’s no evidence of this.”
BackgroundCorticosteroid receptor signalling modes and stress adaptation in the brain
Meijer, O. C. (2011) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci.2011.114
Self-citationEffects of Glucocorticoids on the Brain
Pereira, A. M., Webb, S. M., & Meijer, O. C. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64329-5
Self-citationSpiga, F., Pooley, J. R., Russell, G. M., & Lightman, S. L. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-802175-0.00043-7 · Cited by 2 · see citing works
Schaaf, M. J. M., & Meijer, O. C. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-802175-0.00029-2 · Cited by 1 · see citing works
Self-citation
- Authors
- Sarabdjitsingh, R. A., Isenia, S., Polman, A., Mijalkovic, J., Lachize, S., Datson, N., de Kloet, E. R., & Meijer, O. C.
- Affiliations
- Leiden University (NL)
- Division of Medical Pharmacology, Leiden/Amsterdam Centre for Drug Research/Leiden University Medical Centre, University of Leiden, 2300 RA Leiden, The Netherlands
- Corresponding author
- Sarabdjitsingh, R. Angela
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2010-01-15
- Volume
- 151
- Issue
- 3
- Pages
- 1177-1186
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2153433545
- Cited by
- 97
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 10 · 2016: 7 · 2015: 4 · 2014: 13 · 2013: 8 · 2012: 8
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- 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
- glucocorticoid receptor, mineralocorticoid receptor, glucocorticoid signaling, GILZ, SGK1, hippocampus, receptor saturation, stress response, circadian rhythm disruption
- MeSH terms
- Serum-Glucocorticoid Regulated Kinases, Activity Cycles, Animals, Brain, Corticosterone, Glucocorticoids, Hippocampus, Male, Promoter Regions, Genetic, Receptors, Glucocorticoid, Transcription Factors, Signal Transduction, Down-Regulation, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Receptors, Mineralocorticoid, Gene Expression Profiling, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
