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Glucocorticoid regulation of the circadian clock modulates glucose homeostasis
Open accessAbstract
Circadian clock genes are regulated by glucocorticoids; however, whether this regulation is a direct or secondary effect and the physiological consequences of this regulation were unknown. Here, we identified glucocorticoid response elements (GREs) at multiple clock genes and showed that 3 were directly regulated by the glucocorticoid receptor. We determined that a GRE within the core clock gene Per2 was continuously occupied during rhythmic expression and essential for glucocorticoid regulation of that gene in vivo. We further demonstrated that mice with a genomic deletion spanning this GRE expressed elevated leptin levels and were protected from glucose intolerance and insulin resistance on glucocorticoid treatment but not from muscle wasting. We conclude that Per2 is an integral component of a particular glucocorticoid regulatory pathway and that glucocorticoid regulation of the peripheral clock is selectively required for some actions of glucocorticoids.
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“Resetting of the peripheral clock occurs through well-defined molecular mechanisms that involve direct interaction of glucocorticoids, glucocorticoid response elements and the regulatory regions of core clock genes Bmal1, Cry1, Per1 and Per2 [63, 64].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [64]
Experimental — accuracy not yet measuredIn the citing paper
“Per2 null mice exhibit no glucocorticoid oscillations, indicating that PER2 may also impact glucocorticoid receptor (GR)-dependent glucose metabolism [24,25].”
From Circadian control of glucose metabolism (2014) · cites this paper as [24]
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Citations
Cites
The nuclear receptor superfamily: the second decade
Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schütz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90199-x · Cited by 6,964
Coordination of circadian timing in mammals
Reppert, S. M., & Weaver, D. R. (2002) · Nature · doi:10.1038/nature00965 · Cited by 4,379
Role of leptin in the neuroendocrine response to fasting
Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996) · Nature · doi:10.1038/382250a0 · Cited by 3,117
Obesity and Metabolic Syndrome in Circadian Clock Mutant Mice
Turek, F. W., Joshu, C., Kohsaka, A., Lin, E., Ivanova, G., McDearmon, E., Laposky, A., Losee-Olson, S., Easton, A., Jensen, D. R., et al. (2005) · Science · doi:10.1126/science.1108750 · Cited by 2,485
Abnormal splicing of the leptin receptor in diabetic mice
Lee, G.-H., Proenca, R., Montez, J. M., Carroll, K. M., Darvishzadeh, J. G., Lee, J. I., & Friedman, J. M. (1996) · Nature · doi:10.1038/379632a0 · Cited by 2,327
Chen, H., Charlat, O., Tartaglia, L. A., Woolf, E. A., Weng, X., Ellis, S. J., Lakey, N. D., Culpepper, J., More, K. J., Breitbart, R. E., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81294-5 · Cited by 2,214
Phinney, D. G., & Prockop, D. J. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0637 · Cited by 1,910
Resetting central and peripheral circadian oscillators in transgenic rats
Yamazaki, S., Numano, R., Abe, M., Hida, A., Takahashi, R.-I., Ueda, M., Block, G. D., Sakaki, Y., Menaker, M., & Tei, H. (2000) · Science · doi:10.1126/science.288.5466.682 · Cited by 1,907
Resetting of circadian time in peripheral tissues by glucocorticoid signaling
Balsalobre, A., Brown, S. A., Marcacci, L., Tronche, F., Kellendonk, C., Reichardt, H. M., Schütz, G., & Schibler, U. (2000) · Science · doi:10.1126/science.289.5488.2344 · Cited by 1,859
STEROID RECEPTOR REGULATED TRANSCRIPTION OF SPECIFIC GENES AND GENE NETWORKS
Yamamoto, K. R. (1985) · Annual Review of Genetics · doi:10.1146/annurev.ge.19.120185.001233 · Cited by 1,850
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Items 101–200 of 427
Nuclear Receptors Regulate Intestinal Inflammation in the Context of IBD
Klepsch, V., Moschen, A. R., Tilg, H., Baier, G., & Hermann‐Kleiter, N. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01070 · Cited by 63
Mood‐related central and peripheral clocks
Ketchesin, K. D., Becker‐Krail, D. D., & McClung, C. A. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14253 · Cited by 67
Circadian Rhythms in Cardiovascular Metabolism
Lal, H., Verma, S. K., Wang, Y., Xie, M., & Young, M. E. (2024) · Circulation Research · doi:10.1161/circresaha.123.323520 · Cited by 67
“40,41 Circadian clocks modulate cellular processes over a 24-hour period, through numerous means.”
BackgroundChronic subordination stress phase advances adrenal and anterior pituitary clock gene rhythms
Razzoli, M., Karsten, C. A., Yoder, J. M., Bartolomucci, A., & Engeland, W. C. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00101.2014 · Cited by 58
“Clock gene rhythms were assessed using mPER2::Luciferase (PER2Luc) knockin mice in which in vitro bioluminescence rhythms reflect the Per2 clock gene expression.”
BackgroundVallée, A., Lecarpentier, Y., Guillevin, R., & Vallée, J.-N. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041212 · Cited by 59
“They are called circadian locomotor output cycles kaput (Clock), brain and muscle aryl-hydrocarbon receptor nuclear translocator-like 1 (Bmal1), Period 1 (Per1), Period 2 (Per2), Period 3 (Per3), and Cryptochrome (Cry 1 and Cry 2) [178,179] (Figure 3).”
BackgroundInfluentialLiu, P. Y. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00683 · Cited by 55
“ments are located in the regulatory regions of the core clock genes, and both peripheral clocks and glucocorticoid receptors are present in these tissues (59, 60, 63).”
BackgroundOkubo, N., Minami, Y., Fujiwara, H., Umemura, Y. M., Tsuchiya, Y., Shirai, T., Oda, R., Inokawa, H., Kubo, T., & Yagita, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078306 · Cited by 55
“Previous studies have identified Per1, Per2, and E4bp4 as direct targets of GRs in mice [37].”
BackgroundThe role of clock genes and rhythmicity in the liver
Schmutz, I., Albrecht, U., & Ripperger, J. A. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.05.007 · Cited by 56
“ments (GRE) were identified in several clock genes and GR occupies a GRE within the clock gene Per2 (So et al., 2009).”
InfluentialRegnier, S. M., Kirkley, A. G., Ye, H., El‐Hashani, E., Zhang, X., Neel, B. A., Kamau, W., Thomas, C. C., Williams, A. K., Hayes, E. T., et al. (2014) · Endocrinology · doi:10.1210/en.2014-1668 · Cited by 55
Gilhooley, M. J., Pinnock, S. B., & Herbert, J. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.12.011 · Cited by 54
Pregnancy-induced adaptations of the central circadian clock and maternal glucocorticoids
Wharfe, M. D., Mark, P. J., Wyrwoll, C. S., Smith, J. T., Yap, C., Clarke, M. W., & Waddell, B. J. (2015) · Journal of Endocrinology · doi:10.1530/joe-15-0405 · Cited by 53
“Moreover, the clock gene expression can be regulated by corticosterone, as glucocorticoid response elements are present within the promoter regions of Per1, Per2 and Rev-erba (Balsalobre et al. 2000, Yamamoto et al. 2005, So et al. 2009).”
BackgroundRegulatory Actions of Glucocorticoid Hormones: From Organisms to Mechanisms
Granner, D. K., Wang, J.-C., & Yamamoto, K. R. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-2895-8_1 · Cited by 56
“To date, only a single GBR, which resides some 25 kb downstream of the transcription start site for the Per2 circadian rhythm regulatory gene, has been unequivocally assigned to its target gene [ 133 ].”
BackgroundSelf-citationIkegami, K., Shigeyoshi, Y., & Masubuchi, S. (2020) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.61.3.26 · Cited by 52
Agorastos, A., & Olff, M. (2020) · European Journal of Psychotraumatology · doi:10.1080/20008198.2020.1833644 · Cited by 56
“…creating a temporary uncoupling of the central and peripheral circadian system (Balsalobre, 2000; Kiessling et al., 2010; Le Minh, 2001; Nader et al., 2009; Nicolaides, Charmandari, Kino, & Chrousos, 2017; So et al., 2009; Tahara, Aoyama, & Shibata, 2017; Torra et al., 2000; Yamamoto et al., 2005).”
BackgroundThe Adrenal Cortex and its Disorders
Miller, W. L. (2009) · Wiley eBooks · doi:10.1002/9781444316728.ch13 · Cited by 51
Circadian rhythms and the HPA axis: A systems view
Androulakis, I. P. (2021) · WIREs Mechanisms of Disease · doi:10.1002/wsbm.1518 · Cited by 55
The interplay between stress, circadian clocks, and energy metabolism
Oster, H. (2020) · Journal of Endocrinology · doi:10.1530/joe-20-0124 · Cited by 52
Smith, S. S., Dole, N. S., Franceschetti, T., Hrdlicka, H. C., & Delany, A. M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.737890 · Cited by 49
“The circadian clocks can be directly regulated by glucocorticoid signaling, as the glucocorticoid receptor transcriptionally activates expression of Per1 through a glucocorticoid response element (GRE) in its promoter and Per2 through a GRE in the first intron (16, 40, 41).”
BackgroundGlucocorticoid 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 50
“Their rhythmhowever is also directly implicated in for instance peripheral clock synchronization, neurogenesis, glucose homeostasis, as well as behavioural re-entrainment and stress responsiveness [17–21].”
BackgroundCasey, T., Crodian, J. S., Erickson, E. C., Kuropatwinski, K. K., Gleiberman, A. S., & Antoch, M. P. (2014) · Biology of Reproduction · doi:10.1095/biolreprod.113.116137 · Cited by 48
Woodruff, E. R., Chun, L. E., Hinds, L. R., & Spencer, R. L. (2016) · Endocrinology · doi:10.1210/en.2015-1884 · Cited by 54
The role of the hypothalamic-pituitary-adrenal axis in modulating seasonal changes in immunity
Pierre, K. K., Schlesinger, N., & Androulakis, I. P. (2016) · Physiological Genomics · doi:10.1152/physiolgenomics.00006.2016 · Cited by 50
Morris, H., Gonçalves, C. F., Dudek, M., Hoyland, J. A., & Meng, Q. (2021) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2020-219515 · Cited by 49
Robust circadian rhythms in organoid cultures from PERIOD2::LUCIFERASE mouse small intestine
Moore, S. R., Pruszka, J., Vallance, J. E., Aihara, E., Matsuura, T., Montrose, M. H., Shroyer, N. F., & Hong, C. I. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.014399 · Cited by 46
“The steroid receptor antagonist RU486 has been shown to disrupt circadian rhythms in mesenchymal stem cells (So et al., 2009); therefore, we tested the effects of RU486 on organoid PER2 rhythms in the absence of serum shock.”
BackgroundRegulation of Mammalian Physiology by Interconnected Circadian and Feeding Rhythms
Atger, F., Mauvoisin, D., Weger, B. D., Gobet, C., & Gachon, F. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00042 · Cited by 46
Circadian regulation of hippocampal function is disrupted with corticosteroid treatment
Birnie, M. T., Claydon, M. D. B., Troy, O. R., Flynn, B. P., Yoshimura, M., Kershaw, Y. M., Zhao, Z., Demski-Allen, R. C. R., Barker, G. R. I., Warburton, E. C., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2211996120 · Cited by 52
“S2: Per1, Klf9, Klf15, Sgk1, Zfp189, and Tsc22d3) supports corticosteroidmediated regulation of clock gene expression (37, 38).”
Glucocorticoid Regulation of Clock Gene Expression in the Mammalian Limbic Forebrain
Segall, L. A., & Amir, S. (2010) · Journal of Molecular Neuroscience · doi:10.1007/s12031-010-9341-1 · Cited by 45
“Recent findings have revealed a functional GRE on the Per2 gene that has been shown to directly bind GR, leading to an upregulation in Per2 ( So et al. 2009 ).”
BackgroundMicroRNAs regulate gene plasticity during cold shock in zebrafish larvae
Hung, I. C., Hsiao, Y.-C., Sun, H. S., Chen, T.-M., & Lee, S. (2016) · BMC Genomics · doi:10.1186/s12864-016-3239-4 · Cited by 45
“The per2 gene may have a glucocorticoid response element that responds to glucocorticoid hormones to increase blood glucose [54].”
BackgroundMurayama, Y., Yahagi, N., Takeuchi, Y., Aita, Y., Saber, Z. M., Wada, N., Li, E., Piao, X., Sawada, Y., Shikama, A., et al. (2019) · FEBS Letters · doi:10.1002/1873-3468.13328 · Cited by 43
Circadian Rhythms in Liver Physiology and Liver Diseases
Tong, X., & Yin, L. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120017 · Cited by 50
Sánchez‐Bretaño, A., Callejo, M., Montero, M., Alonso-Gómez, A. L., Delgado, M. J., & Isorna, E. (2015) · Journal of Comparative Physiology B · doi:10.1007/s00360-015-0936-2 · Cited by 43
“Similarly, endogenous signals that increase Per1 (e.g., glucocorticoids) could shift the phase of clock gene expression, as it is suggested in different mammalian cell lines (Balsalobre et al. 2000; So et al. 2009).”
BackgroundResultInfluentialCalabrese, F., Savino, E., Papp, M., Molteni, R., & Riva, M. A. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.12.023 · Cited by 47
“Since a canonical GRE is present in the promoter region of the Per1 gene, while an intronic GRbinding sequence confers GC responsiveness to Per2 (18), the effects observed on GR protein levels may contribute to the alterations found in Per’s mRNA levels.”
BackgroundMavroudis, P. D., Corbett, S., Calvano, S. E., & Androulakis, I. P. (2014) · Mathematical Biosciences · doi:10.1016/j.mbs.2014.10.006 · Cited by 42
“In the present work, in accordance with our previous modeling efforts [42], we incorporate the entrainment of peripheral immune cells by cortisol by considering the binding of glucocorticoid/receptor complex to the GRE present at the promoter region of Per and Cry clock genes (Equation 9, last additive term) [43, 44].”
Repeated psychosocial stress at night, but not day, affects the central molecular clock
Bartlang, M. S., Savelyev, S. A., Johansson, A., Reber, S. O., Helfrich‐Förster, C., & Lundkvist, G. B. S. (2014) · Chronobiology International · doi:10.3109/07420528.2014.940085 · Cited by 43
“GCs, in turn, stimulate the expression of several clock genes, including Per2, via the glucocorticoid-responsive element (GRE), in liver, heart and kidney (So et al., 2009; Yamamoto et al., 2005).”
BackgroundA rotating light cycle promotes weight gain and hepatic lipid storage in mice
Christie, S., Vincent, A. D., Li, H., Frisby, C. L., Kentish, S. J., O’Rielly, R., Wittert, G., & Page, A. J. (2018) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00020.2018 · Cited by 41
“In healthy conditions, these ZTs are highly synchronized, facilitating coordination and efficiency of metabolic processes and promoting a healthy state of energy homeostasis (53).”
BackgroundDoi, M., Shimatani, H., Atobe, Y., Murai, I., Hayashi, H., Takahashi, Y., Fustin, J., Yamaguchi, Y., Kiyonari, H., Koike, N., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10532-2 · Cited by 42
Glucocorticoids and Brown Adipose Tissue: Do glucocorticoids really inhibit thermogenesis?
Luijten, I. H. N., Cannon, B., & Nedergaard, J. (2019) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2019.07.002 · Cited by 44
Peripheral circadian clocks are diversely affected by adrenalectomy
Soták, M., Bryndová, J., Ergang, P., Vagnerová, K., Kvapilová, P., Vodička, M., Pácha, J., & Sumová, A. (2016) · Chronobiology International · doi:10.3109/07420528.2016.1161643 · Cited by 40
“The effect of glucocorticoids on Per1 appears to occur directly through the GRE in the Per1 gene (Yamamoto et al., 2005; Koyanagi et al., 2006; So et al., 2009); however, the direct effect of glucocorticoids on other genes cannot be excluded.”
BackgroundResultInfluentialA wheel of time: the circadian clock, nuclear receptors, and physiology: Figure 1.Preprint
Yang, X. (2010) · Genes & Development · doi:10.1101/gad.1920710 · Cited by 43
“Wee1 and c-Myc are directly regulated by the molecular clock via the E-box elements at their promoters and, as a result, their expression is severely disturbed in mice deficient in Clock, Cry, or Per2.”
BackgroundInfluentialCircadian Plasticity in the Brain of Insects and Rodents
Krzeptowski, W., Hess, G., & Pyza, E. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00032 · Cited by 42
“…brain responsible for maintaining circadian rhythms, transplantations (AguilarRoblero et al., 1986; Lehman et al., 1987; Ralph et al., 1990; Sollars et al., 1995; Sujino et al., 2003) and surgical lesions (Moore and Eichler, 1972; Stephan and Zucker, 1972; Mouret et al., 1978) of the…”
BackgroundHartsock, M. J., & Spencer, R. L. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.07.023 · Cited by 52
Brain-Specific Homeobox Factor as a Target Selector for Glucocorticoid Receptor in Energy Balance
Lee, B., Kim, S.-G., Kim, J., Choi, K. Y., Lee, S., Lee, S., & Lee, J. W. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00094-13 · Cited by 38
“(F) Sequences of AgRP-GRE, Per1-GRE, and Asb4-GRE as well as of MMTV-GRE and other known GREs that are negatively regulated by Bsx are shown.”
BackgroundInfluentialAlmeida, S., Madalena Chaves, A., & Delaunay, F. (2019) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2019.110015 · Cited by 37
Capelle, C., Chen, A., Zeng, N., Baron, A., Grzyb, K., Arns, T., Skupin, A., Ollert, M. W., & HeFeng, F. Q. (2022) · Immunology · doi:10.1111/imm.13448 · Cited by 39
Clockwork allergy: How the circadian clock underpins allergic reactions
Nakao, A. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2018.08.007 · Cited by 40
Integration of Melatonin Related Redox Homeostasis, Aging, and Circadian Rhythm
Yanar, K., Simsek, B., & Çakatay, U. (2018) · Rejuvenation Research · doi:10.1089/rej.2018.2159 · Cited by 37
“14 15–17 These various systems’ wide effects are involved in the most fundamentally ingrained homeostatic systems of the organism, and their disruption is implicated in a wide ranging spectrum of disorders, such as sleep disorders, cancer, and cardiovascular disease.”
Engel, K. B., & Yamamoto, K. R. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05351-11 · Cited by 41
“antibody were performed as previously described (42).”
Self-citationZhen, Y., Ge, L., Xu, Q., Hu, L., Wei, W., Huang, J., Loor, J. J., Yang, Q., Wang, M., & Zhou, P. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.848248 · Cited by 36
“Per2-KO mice lack a glucocorticoid rhythm and diurnal feeding rhythm, which can lead to obesity when fed a high-fat diet (9, 51).”
BackgroundMavroudis, P. D., Corbett, S., Calvano, S. E., & Androulakis, I. P. (2014) · Physiological Genomics · doi:10.1152/physiolgenomics.00026.2014 · Cited by 36
van Lierop, M.-J. C., Alkema, W. B. L., Laskewitz, A. J., Dijkema, R., van der Maaden, H. M., Smit, M. J., Plate, R., Conti, P. G. M., Jans, C. G. J. M., Timmers, C. M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048385 · Cited by 35
“Another interesting gene is Per-2, which belongs to the class of circadian clock genes and has recently been described as a primary GR target gene involved in glucose homeostasis [38].”
BackgroundParnell, A. A., Nobrega, A. K. D., & Lyons, L. C. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109904 · Cited by 34
Should we listen to our clock to prevent type 2 diabetes mellitus?
Ramanujam, K., Marimuthu, G., Spence, D. W., Pandi-Perumal, S. R., BaHammam, A. S., Brown, G. M., & Cardinali, D. P. (2014) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2014.07.029 · Cited by 37
Implications of circadian rhythm and stress in addiction vulnerability
Becker‐Krail, D. D., & McClung, C. A. (2016) · F1000Research · doi:10.12688/f1000research.7608.1 · Cited by 35
“Both Period genes are afforded this unique relationship with glucocorticoids due to the presence of GREs in their promotor regions (So et al., 2009; Yamamoto et al., 2005).”
Casey, T., & Plaut, K. I. (2022) · Journal of Animal Science · doi:10.1093/jas/skac233 · Cited by 40
“Molecular redundancy exists for all core clock genes with three PER (PER1, PER2, PER3) and two CRY (CRY1, CRY2) genes, and paralogues of BMAL1 and CLOCK being BMAL2 and NPAS2.”
BackgroundInfluentialDiurnal rhythms are altered in a mouse model of multiple sclerosis
Buenafe, A. C. (2011) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2011.12.002 · Cited by 34
“Glucocorticoids (GCs) are produced in a rhythmic pattern governed by the SCN and adrenal clocks and have been proposed to play a major role in synchronizing the peripheral clocks (Balsalobre et al., 2000; Dickmeis, 2009; So et al., 2009).”
BackgroundAn Endocrinologist's Guide to the Clock
Prasai, M., Pernicova, I., Grant, P. J., & SCOTT, E. M. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2449 · Cited by 35
Singh, N., Dalal, V., & Kumar, P. (2019) · Molecular Simulation · doi:10.1080/08927022.2019.1662002 · Cited by 35
Verlande, A., Chun, S. K., Goodson, M. O., Fortin, B. M., Bae, H., Jang, C., & Masri, S. (2021) · Science Advances · doi:10.1126/sciadv.abf3885 · Cited by 35
“Glucocorticoids also promote gluconeogenesis through CRY-mediated repression of the glucocorticoid receptor (40, 41), and several clock proteins regulate nuclear receptors to control circadian metabolic gene expression programs (42).”
BackgroundInteractions between psychosocial stress and the circadian endogenous clock
Helfrich‐Förster, C. (2017) · PsyCh Journal · doi:10.1002/pchj.202 · Cited by 33
Transcriptional glucocorticoid effects in the brain: Finding the relevant target genes
Meijer, O. C., Buurstede, J. C., Viho, E. M. G., Amaya, J. M., Koning, A.-S. C. A. M., van der Meulen, M., van Weert, L. T. C. M., Paul, S. N., Kroon, J., & Koorneef, L. L. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13213 · Cited by 34
Phase-dependent resetting of the adrenal clock by ACTH in vitro
Yoder, J. M., Brandeland, M. A., & Engeland, W. C. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00519.2013 · Cited by 30
“Since rhythmic glucocorticoids are critical for maintaining homeostasis by controlling glucose metabolism (46), entrainment of other peripheral clocks (2, 22, 36) and regulating clock gene rhythms in brain nuclei implicated in control of motivation and emotional states (44), acute stress could have persistent deleteri…”
BackgroundHernández-Pérez, J., Naderi, F., Chivite, M., Soengas, J. L., Míguez, J. M., & López‐Patiño, M. A. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00611 · Cited by 34
“…cortisol was reported for different fish species (Cerdá-Reverter et al., 1998; Pavlidis et al., 1999; Small, 2005; Ebbesson et al., 2008) and even related with feeding and metabolism, suggesting a possible synchronization of the cortisol secretion with feeding time (Spieler and Noeske, 1984).”
BackgroundChronobiology and Chronotherapy of Osteoporosis
Winter, E. M., Kooijman, S., Appelman‐Dijkstra, N. M., Meijer, O. C., Rensen, P. C. N., & Schilperoort, M. (2021) · JBMR Plus · doi:10.1002/jbm4.10504 · Cited by 33
Noguchi, T., Ikeda, M., Ohmiya, Y., & Nakajima, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037093 · Cited by 32
“is directly controlled by glucocorticoids [56].”
The Liver in the Eyes of a Chronobiologist
Zwighaft, Z., Reinke, H., & Asher, G. (2016) · Journal of Biological Rhythms · doi:10.1177/0748730416633552 · Cited by 29
“CRY proteins use alternative mechanisms by interacting either with G protein–coupled receptors or glucocorticoid receptor to control gluconeogenesis in the liver (So et al., 2009; Lamia et al., 2011).”
BackgroundShirato, K., & Sato, S. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.826738 · Cited by 31
Circadian Regulation in Tissue Regeneration
Paatela, E., Munson, D., & Kikyo, N. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092263 · Cited by 29
“Corticosterone undergoes circadian patterning and peaks at the onset of darkness in mice, reaching a nadir at dawn [75,82].”
BackgroundQuattrocelli, M., Wintzinger, M., Miz, K., Levine, D. C., Peek, C. B., Bass, J. T., & McNally, E. M. (2022) · Science Advances · doi:10.1126/sciadv.abm1189 · Cited by 30
“The regulatory region cloned in this reporter construct does not contain the GR-binding sites for Per2 (12).”
BackgroundInfluentialKiss, Z., & Ghosh, P. (2016) · Endocrine Related Cancer · doi:10.1530/erc-16-0366 · Cited by 31
“function, but in addition, it was shown that Per2 contains glucocorticoid response elements and can interact with PPAR γ (So et al .”
InfluentialCircadian regulation of digestive and metabolic tissues
Taleb, Z., & Karpowicz, P. A. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00166.2022 · Cited by 30
Wyse, C. A., Zhang, X., McLaughlin, M., Biello, S. M., Hough, D., Bellingham, M., Curtis, A. M., Robinson, J. E., & Evans, N. P. (2018) · Physiology & Behavior · doi:10.1016/j.physbeh.2018.06.001 · Cited by 30
“Furthermore, transcription of the clock genes, per1, per2, e4bp4 and timeless was directly regulated by glucocorticoid receptor binding, supporting overall regulation of circadian timing by glucocorticoid signalling [45].”
van der Veen, D. R., Shao, J., Yang, X., Li, L., & Duffield, G. E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047692 · Cited by 29
“Both the per1 and per2 genes contain glucocorticoid receptor binding sequences, making direct interaction between the glucocorticoid receptor and each gene promoter possible, and may be indicative that per1 and per2 are sites of action for DEX to alter the circadian clock [25].”
BackgroundInfluentialMECHANISMS IN ENDOCRINOLOGY: Does circadian and ultradian glucocorticoid exposure affect the brain?
Kalafatakis, K., Russell, G. M., & Lightman, S. L. (2018) · European Journal of Endocrinology · doi:10.1530/eje-18-0853 · Cited by 29
Wharfe, M. D., Wyrwoll, C. S., Waddell, B. J., & Mark, P. J. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00060.2016 · Cited by 32
Perinatal Programming of Circadian Clock-Stress Crosstalk
Astiz, M., & Oster, H. (2018) · Neural Plasticity · doi:10.1155/2018/5689165 · Cited by 31
“Time-of-day information is translated from the clock machinery into physiological signals through rhythmic regulation of downstream clock-controlled genes [32].”
BackgroundInfluentialNegri, M., Pivonello, C., Simeoli, C., Gennaro, G. D., Venneri, M. A., Sciarra, F., Ferrigno, R., de Angelis, C., Sbardella, E., Martino, M. C. D., et al. (2020) · Neuroendocrinology · doi:10.1159/000512685 · Cited by 27
The sleep-wake distribution contributes to the peripheral rhythms in PERIOD-2
Hoekstra, M. M., Jan, M., Katsioudi, G., Emmenegger, Y., & Franken, P. (2021) · eLife · doi:10.7554/elife.69773 · Cited by 30
Role of Omega-3 Fatty Acids as Non-Photic Zeitgebers and Circadian Clock Synchronizers
Checa-Ros, A., & D’Marco, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012162 · Cited by 28
“This autonomic pathway modulates the sensitivity of the adrenal gland to the adrenocorticotropic hormone (ACTH) as well as the release of glucocorticoids [12,13], which act as humoral entraining signals for peripheral clocks [14,15].”
BackgroundCircadian rhythms in white adipose tissue
van der Spek, R., Kreier, F., Fliers, E., & Kalsbeek, A. (2012) · Progress in brain research · doi:10.1016/b978-0-444-59427-3.00011-3 · Cited by 30
“, 2000), by binding to the glucocorticoids response element in the promotor region of Period1 (Per1) and possibly Period2 (Per2) (Balsalobre et al., 2000; So et al., 2009; Yamamoto et al., 2005).”
BackgroundSegall, L. A., & Amir, S. (2010) · Journal of Molecular Neuroscience · doi:10.1007/s12031-010-9375-4 · Cited by 28
“Though most findings have revealed a functional GRE site in the promoter of Per1, a recent report has demonstrated the induction of Per2 via GR binding to a GRE site in the promoter region of Per2 in mesenchymal stem cells (So et al. 2009).”
BackgroundCircadian rhythm of intraocular pressure
Ikegami, K. (2024) · The Journal of Physiological Sciences · doi:10.1186/s12576-024-00905-8 · Cited by 28
“In contrast, GCT promotes the expression of several genes through glucocorticoid-response elements (GREs) [87], but it modulates Adrb2 expression through the pro-motor GRE [88].”
BackgroundMechanisms of hormonal regulation of the peripheral circadian clock in the colon
Polidarová, L., Houdek, P., Sládek, M., Novosadová, Z., Pácha, J., & Sumová, A. (2016) · Chronobiology International · doi:10.1080/07420528.2016.1231198 · Cited by 28
“…directly via GRE in the Per2 promoter but more likely also by a combinatory indirect effect via GREs in other clock genes (Per1, Nfil3/E4bp4) (So et al., 2009) and due to the sensitivity of activated glucocorticoid receptors to CLOCK- (Nader et al., 2009) and CRY-mediated repression (Lamia…”
BackgroundInfluentialCross-species physiological interactions of endocrine disrupting chemicals with the circadian clock
Bottalico, L. N., & Weljie, A. M. (2020) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2020.113650 · Cited by 30
Circadian Clocks and the Interaction between Stress Axis and Adipose Function
Kolbe, I., Dumbell, R., & Oster, H. (2015) · International Journal of Endocrinology · doi:10.1155/2015/693204 · Cited by 27
“By restricting food access to the light phase, core clock genes such as Per1, Per2, Per3, Reverb𝛼, and Cry1 and clock output genes such as Dbp and Cyp2a5 are phase shifted by 8–12 h in the liver independent of SCN Per1/2 expression.”
BackgroundChen, G., Tang, Q., Yu, S., Shen, Y., Sun, J., Peng, J., Yin, Y., Feng, G., Lu, X., Mei, G., et al. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01152-x · Cited by 27
What is the best approach to tailoring hydrocortisone dose to meet patient needs in 2012?
Debono, M., & Ross, R. J. M. (2012) · Clinical Endocrinology · doi:10.1111/cen.12117 · Cited by 26
Dantec, Y. L., Hache, G., Guilloux, J., Guiard, B. P., David, D. J. P., Adrien, J., & Escourrou, P. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.05.050 · Cited by 30
“These receptors are known to control molecular clock gene expression showing positive (GRE) or negative (nGRE) glucocorticoid-responsive elements (So et al., 2009; Surjit et al., 2011).”
Tortonese, D. J., Preedy, D., Hesketh, S. A., Webb, H., Wilkinson, E. S., Allen, W. R. T., Fuller, C. J., Townsend, J. S., & Short, R. V. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02222.x · Cited by 25
Su, Y., Foppen, E., Zhang, Z., Fliers, E., & Kalsbeek, A. (2015) · Genes to Cells · doi:10.1111/gtc.12315 · Cited by 26
Wu, T., Jiang, J., Yang, L., Li, H., Zhang, W., Chen, Y., Zhao, B., Kong, B., Lü, P., Zhao, Z., et al. (2016) · Chronobiology International · doi:10.1080/07420528.2016.1238831 · Cited by 25
“Although the roles of oscillations in GC secretion are not well understood, they are thought to be important for endogenous homeostasis (So et al., 2009), and disrupted endogenous rhythms can lead to a range of metabolic and even”
BackgroundFan, J. R., Jiang, X., Hu, Y., Si, Y., Ding, L., & Wu, W. (2013) · Biomaterials Science · doi:10.1039/c2bm00162d · Cited by 25
Clock Genes, Metabolism, and Cardiovascular Risk
Tarquini, R., & Mazzoccoli, G. (2017) · Heart Failure Clinics · doi:10.1016/j.hfc.2017.05.001 · Cited by 26
“Glucocorticoids control glucose homeostasis and circadian rhythmicity modulating the expression of core clock genes, specifically Per1 and Per2, through binding via GRs to glucocorticoid response elements in their promoters.(75,76) GR levels oscillate with 24hour periodicity in metabolically active tissues, in particu…”
BackgroundSexual Differentiation of Circadian Clock Function in the Adrenal Gland
Kloehn, I., Pillai, S. B., Officer, L., Klement, C., Gasser, P. J., & Evans, J. A. (2016) · Endocrinology · doi:10.1210/en.2015-1968 · Cited by 27
Cushing Syndrome, Hypercortisolism, and Glucose Homeostasis: A Review
DeFronzo, R. A., & Auchus, R. J. (2025) · Diabetes · doi:10.2337/db25-0120 · Cited by 31
Circadian clocks and adaptive immune function: from mechanisms to therapeutic applications
Szredzka, A., Chwastowicz, A., Pergoł, J. K., & Matryba, P. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1697854 · Cited by 29
E4BP4 mediates glucocorticoid-regulated adipogenesis through COX2
Yang, Y., Wei, H., Song, T., Cai, A., Zhou, Y., Peng, J., Jiang, S., & Peng, J. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.04.015 · Cited by 23
Chun, L. E., Christensen, J., Woodruff, E. R., Morton, S. J., Hinds, L. R., & Spencer, R. L. (2017) · Stress · doi:10.1080/10253890.2017.1404571 · Cited by 24
“The Per2 and Bmal1 genes are also associated with putative GRE sequences (Cheon, Park, Cho, & Kim, 2013; Reddy et al., 2007; So et al., 2009), but they have not been found to be rapidly increased in vivo by glucocorticoids (Yamamoto et al., 2005).”
BackgroundStress alters the transcriptional activity of Leydig cells dependently on the diurnal time
Medar, M. L., Andrić, S. A., & Kostic, T. S. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111469 · Cited by 22
Glucocorticoids Reset the Nasal Circadian Clock in Mice
Honma, A., Yamada, Y., Nakamaru, Y., Fukuda, S., Honma, K., & Honma, S. (2015) · Endocrinology · doi:10.1210/en.2015-1490 · Cited by 23
Oscillators entrained by food and the emergence of anticipatory timing behaviors
Silver, R., & Balsam, P. D. (2010) · Sleep and Biological Rhythms · doi:10.1111/j.1479-8425.2010.00438.x · Cited by 25
Metadata
- Authors
- So, A. Y.-L., Bernal, T. U., Pillsbury, M. L., Yamamoto, K. R., & Feldman, B. J.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-10-13
- Volume
- 106
- Issue
- 41
- Pages
- 17582-17587
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2757402
- OpenAlex
- W1998522501
- Cited by
- 431
- References
- 51
- Citations by year
- 2026: 15 · 2025: 26 · 2024: 37 · 2023: 19 · 2022: 36 · 2021: 28 · 2020: 32 · 2019: 28 · 2018: 22 · 2017: 28 · 2016: 33 · 2015: 23 · 2014: 25 · 2013: 20 · 2012: 18
- FWCI
- 8.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- University of California, San Francisco
- National Cancer Institute (CA20535, R01CA020535, R37CA020535)
- National Institute of General Medical Sciences (R25GM056847, GM 56847)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK073697, DK73697)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- glucocorticoids, circadian clock, clock genes, glucocorticoid response element, glucocorticoid receptor, Per2, glucose homeostasis, insulin resistance, impaired glucose tolerance, leptin, muscle atrophy, peripheral clocks
- MeSH terms
- Animals, Circadian Rhythm, Gene Expression Regulation, Glucocorticoids, Glucose, Homeostasis, Nuclear Proteins, Transcription Factors, Transcription, Genetic, Polymerase Chain Reaction, Cell Cycle Proteins, Leptin, Mice, Period Circadian Proteins, Mesenchymal Stem Cells
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