The DOI matches its Crossref record; 48 of the 49 references it cites were found in a registry or an index.
Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress
Abstract
The stress system coordinates the adaptive responses of the organism to stressors of any kind.(1). The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic beta-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholaminergic input. The end-hormones of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LC/NE and beta-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5' deiodinase, which converts the relatively inactive tetraiodothyronine (T(4)) to triiodothyronine (T(3)), contributing further to the suppression of reproductive, growth and thyroid functions. They also have direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome X) and direct effects on the bone, causing "low turnover" osteoporosis. Central CRH, via glucocorticoids and catecholamines, inhibits the inflammatory reaction, while directly secreted by peripheral nerves CRH stimulates local inflammation (immune CRH). CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above. Conversely, potentiators of CRH secretion/action may be useful to treat atypical depression, postpartum depression and the fibromyalgia/chronic fatigue syndromes, all characterized by low HPA axis and LC/NE activity, fatigue, depressive symptomatology, hyperalgesia and increased immune/inflammatory responses to stimuli.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the brain, glucocorticoids interact with high-affinity mineralocorticoid receptors and lower affinity glucocorticoid receptors (Herman et al., 2016;Smith and Vale, 2006;Tsigos and Chrousos, 2002).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Tsigos and Chrousos, 2002
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Such beliefs engender misdirected coping behavior and have profound physiological consequences, including a dysregulation of cerebral control over endocrine and autonomic nervous system processes (e.g., aberrant activation of the hypothalamic-pituitary axis; HPA; Tsigos and Chrousos, 2002).”
From Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression (2016) · cites this paper as Tsigos and Chrousos, 2002
Experimental — accuracy not yet measuredIn the citing paper
“The vagal afferent pathways are involved in the activation/regulation of the HPA axis (29), which coordinates the adaptive responses of the organism to stressors of any kind (30).”
From Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders (2018) · cites this paper as [30]
In the citing paper
“An important interplay is also the excitatory reciprocal interaction between the HPA axis and the brainstem sympathetic locus coeruleus (LC)-norepinephrine (NE) system: CRH activates the LC; in turn, NE, a known wake-promoting neurotransmitter, activates hypothalamic CRH [9, 10].”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [9]
In the citing paper
“acteristic frequencies: ultradian oscillations, with a period of 20-120 min [4-6] superimposed on circadian oscillations, with a period of about 24 h.”
From Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress (2011) · cites this paper as [5]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A Syndrome produced by Diverse Nocuous Agents
Selye, H. (1936) · Nature · doi:10.1038/138032a0 · Cited by 3,967
Vale, W., Spiess, J., Rivier, C., & Rivier, J. (1981) · Science · doi:10.1126/science.6267699 · Cited by 3,965
Vale, W., Spiess, J., RIVIER, C. L., & Rivier, J. (1982) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-198205000-00013 · Cited by 3,904
The Concepts of Stress and Stress System Disorders: Overview of Physical and Behavioral Homeostasis
Chrousos, G. P. (1992) · JAMA · doi:10.1001/jama.1992.03480090092034 · Cited by 2,689
Self-citationThe Hypothalamic–Pituitary–Adrenal Axis and Immune-Mediated Inflammation
Chrousos, G. P. (1995) · New England Journal of Medicine · doi:10.1056/nejm199505183322008 · Cited by 2,579
Self-citationClinical and Biochemical Manifestations of Depression
Gold, P. W., Goodwin, F. K., & Chrousos, G. P. (1988) · New England Journal of Medicine · doi:10.1056/nejm198808183190706 · Cited by 1,057
Self-citationSmith, G. W., Aubry, J.-M., Dellu, F., Contarino, A., Bilezikjian, L. M., Gold, L. H., Chen, R., Marchuk, Y., Hauser, C., Bentley, C. A., et al. (1998) · Neuron · doi:10.1016/s0896-6273(00)80491-2 · Cited by 892
Brain corticosteroid receptor balance and homeostatic control
de Kloet, E. R. (1991) · Frontiers in Neuroendocrinology · Cited by 842
Scheinman, R. I., Gualberto, A., Jewell, C. M., Cidlowski, J. A., & Baldwin, A. S. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.2.943 · Cited by 819
Rivier, C., & Rivest, S. (1991) · Biology of Reproduction · doi:10.1095/biolreprod45.4.523 · Cited by 799
Cited by
Sorted by citations
Items 701–800 of 1,016
Teilmann, A. C., Kalliokoski, O., Sørensen, D. B., Hau, J., & Abelson, K. (2014) · Laboratory Animals · doi:10.1177/0023677214541438 · Cited by 42
“Regardless of the sampling method, manual blood sampling will inevitably cause a stress response from the vascular puncture as well as from the handling and restraint of the animal,(11,12) which may affect the experimental outcome.(13) A relatively new technique for repeated blood sampling in mice is automated blood s…”
MethodEnvironmental impacts on fish mucosa
Sundh, H., & Sundell, K. S. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-417186-2.00007-8 · Cited by 44
Simultaneous HPLC-APCI-MS/MS quantification of endogenous cannabinoids and glucocorticoids in hair
Mwanza, C., Zheng, C., Zhang, Q., Chen, S., Wang, W., & Deng, H. (2016) · Journal of Chromatography B · doi:10.1016/j.jchromb.2016.06.002 · Cited by 42
Chi, Y., Zhang, W., Yang, F., Su, F., & Zhou, Y. (2019) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x19500745 · Cited by 42
Sleep–wake regulation in preterm and term infants
Georgoulas, A., Jones, L., Laudiano‐Dray, M. P., Meek, J. H., Lorenzo Fabrizi, D., & Whitehead, K. (2020) · SLEEP · doi:10.1093/sleep/zsaa148 · Cited by 42
“There is reciprocal stimulation between CRH release and locus coeruleus firing [82, 83], and between CRH release and the orexinergic neuronal activity, which reinforces locus coeruleus firing [84–90].”
BackgroundPsychological Co-morbidities of Physical Illness
Pagoto, S. (2011) · Springer eBooks · doi:10.1007/978-1-4419-0029-6 · Cited by 44
Schubert, C., Geser, W., Noisternig, B., Fuchs, D., Welzenbach, N., König, P., Schüßler, G., Ocaña‐Peinado, F. M., & Lampe, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029415 · Cited by 41
“gonadal, growth, thyroid and immune systems [1], and that its”
BackgroundWayhs, C. A. Y., Manfredini, V., Sitta, Â., Deon, M., Ribas, G. S., Vanzin, C. S., Biancini, G. B., Ferri, M. K., Nin, M. S., Barros, H. M. T., et al. (2010) · Metabolic Brain Disease · doi:10.1007/s11011-010-9211-0 · Cited by 41
“It has been hypothesized that depressionmaybeassociatedwithinsulinresistancesecondary to hypercortisolism, based on the effect of elevated plasma glucocorticoid levels to decrease insulin sensitivity ( Tsigos and Chrousos 2002; Vogelzangs et al. 2007).”
BackgroundMissing and Possible Link between Neuroendocrine Factors, Neuropsychiatric Disorders, and Microglia
Kato, T. A., Hayakawa, K., Monji, A., & Kanba, S. (2013) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2013.00053 · Cited by 43
Defensive responses of Brandt's voles (Lasiopodomys brandtii) to stored cat feces
Hegab, I. M., Jin, Y., Ye, M., Wang, A., Yin, B., Yang, S., & Wei, W. (2013) · Physiology & Behavior · doi:10.1016/j.physbeh.2013.10.030 · Cited by 41
Wasinski, F., Gregnani, M. F., Ornellas, F. H., Bacurau, A. V. N., Câmara, N. O. S., Araújo, R. C., & Bacurau, R. F. P. (2014) · Mediators of Inflammation · doi:10.1155/2014/326803 · Cited by 42
Cortés, R., Teles, M., Oliveira, M., Fierro-Castro, C., Tort, L., & Cerdá‐Reverter, J. M. (2017) · Fish Physiology and Biochemistry · doi:10.1007/s10695-017-0431-7 · Cited by 41
Herane-Vives, A., de Angel, V., Papadopoulos, A. S., Wise, T., Chua, K., Strawbridge, R., Castillo, D., Arnone, D., Young, A. H., & Cleare, A. J. (2018) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12852 · Cited by 43
“Other research has suggested that participants with atypical depression have hyposecreation of corticotropin-releasing factor (68).”
BackgroundObjective detection of chronic stress using physiological parameters
Abdi, R. M. A., Alhitary, A. E., Abdulhay, E., & Al‐Bashir, A. K. (2018) · Medical & Biological Engineering & Computing · doi:10.1007/s11517-018-1854-8 · Cited by 44
Ganesan, S. M., Vazana, S., & Stuhr, S. H. (2021) · Periodontology 2000 · doi:10.1111/prd.12390 · Cited by 44
Monteleone, P., Tortorella, A. A. V., Scognamiglio, P., Serino, I., Monteleone, A. M., & Maj, M. (2012) · Neuropsychobiology · doi:10.1159/000341877 · Cited by 41
Ferri, C. C., & Ferguson, A. V. (2005) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2005.01336.x · Cited by 41
Daskalopoulos, E. P., Malliou, F., Rentesi, G., Μαρσέλος, Μ., Lang, M. A., & Konstandi, M. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00545.2011 · Cited by 41
“It is well defined that stimulation of ARs has a negative control on hypothalamic GH-releasing hormone and finally on GH release from the pituitary thus negatively affecting STAT5b activation (68, 49, 67), an event that in turn downregulates the above-mentioned CYPs (26, 64, 74).”
BackgroundMuhtz, C., Godemann, K., von Alm, C., Wittekind, C., Goemann, C., Wiedemann, K., Yassouridis, A., & Kellner, M. (2011) · Journal of Nervous & Mental Disease · doi:10.1097/nmd.0b013e318229cfba · Cited by 40
“It has been demonstrated that a downregulated glucocorticoid system may result in elevations in leukocyte and other immune inflammatory activities (Tsigos and Chrousos, 2002; von Kanel et al., 2007; Yehuda et al., 2004), which could arise in higher levels of highly sensitive C-reactive protein (h-CRP; Spitzer et al.”
BackgroundMolecular mechanisms linking stress and insulin resistance
Yaribeygi, H., Maleki, M., Butler, A. E., Jamialahmadi, T., & Sahebkar, A. (2021) · EXCLI journal · doi:10.17179/excli2021-4382 · Cited by 59
Li, J., Liu, F., Liu, Z., Li, M., Wang, Y., Shang, Y., & Li, Y. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-05875-0 · Cited by 46
“The association between the menstrual cycle and depression could be supported by a possible biological mechanism, the hypothalamic‒pituitary‒adrenal axis, which is implicated in playing a role in regulating mood and responding to stress [103–105].”
BackgroundChan, H., Chang, C., Chiang, S. C., Chen, J., Chen, C., Sun, H., Hwu, H., & Lai, M. (2008) · Journal of Psychopharmacology · doi:10.1177/0269881108096070 · Cited by 39
Armon, G. (2009) · Stress and Health · doi:10.1002/smi.1266 · Cited by 40
Au, B., Smith, K. J., Gariépy, G., & Schmitz, N. (2014) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2014.07.012 · Cited by 41
Neufeld-Cohen, A., Kelly, P. A. T., Paul, E. D., Carter, R. N., Skinner, E. M., Olverman, H. J., Vaughan, J. M., Issler, O., Kuperman, Y., Lowry, C. A., et al. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.05.005 · Cited by 41
Emotion: the Self-regulatory Sense
Kauffman, K. P. (2014) · Global Advances in Health and Medicine · doi:10.7453/gahmj.2013.058 · Cited by 48
Chen, H. C., Spiers, J. G., Sernia, C., & Lavidis, N. A. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.11.023 · Cited by 41
Martin, W., Murray, P. S., Bates, P. R., & Lee, P. S. Y. (2016) · Aviation Psychology and Applied Human Factors · doi:10.1027/2192-0923/a000092 · Cited by 44
Testosterone and cortisol responses in male soccer players: The effect of home and away venues
Fothergill, M. A., Wolfson, S., & Neave, N. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.04.021 · Cited by 42
“It is also well established that the hypothalamic-pituitary-adrenal (HPA) axis reacts to both physical and psychological stressors by increasing C [13, 25].”
Dai, X., Liu, B., Ai, S., Nie, X., Xu, Q., Hu, J., Zhang, Q., Xu, Y., Zhang, Z., & Lu, G. (2019) · Brain Imaging and Behavior · doi:10.1007/s11682-019-00064-0 · Cited by 40
Effects of social isolation and environmental enrichment on atherosclerosis in ApoE−/−mice
Bernberg, E., Andersson, I. J., Gan, L., Naylor, A. S., Johansson, M. E., & Bergström, G. M. L. (2008) · Stress · doi:10.1080/10253890701824051 · Cited by 40
Comparative study of perturbations of peripheral markers in different stressors in rats
Rai, D., Bhatia, G., Sen, T., & Palit, G. (2003) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y03-117 · Cited by 40
“Stress directly inhibits pituitary gonadotropin, growth hormone (GH), and thyroid-stimulating hormone (TSH) secretion and has direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia, and hypertension (metabolic syndrome X) (Tsigos and Chro…”
BackgroundSocial isolation stress impairs passive avoidance learning in senescence-accelerated mouse (SAM)
Chida, Y., Sudo, N., Mori, J., & Kubo, C. (2005) · Brain Research · doi:10.1016/j.brainres.2005.10.042 · Cited by 40
Skouen, J. S., Smith, A. J., Warrington, N. M., O’Sullivan, P., McKenzie, L., Pennell, C. E., & Straker, L. M. (2012) · European Journal of Pain · doi:10.1002/j.1532-2149.2012.00131.x · Cited by 41
“Neurotransmitters linked to the HPA axis involved in the transmission of painful stimuli as well as stress responses are thought to mediate these changes (Tsigos and Chrousos, 2002; Hocking et al., 2010).”
BackgroundYao, M., Stenzel‐Poore, M. P., & Denver, R. J. (2007) · Endocrinology · doi:10.1210/en.2006-1413 · Cited by 40
“Besides the hypophysiotropic function of hypothalamic CRF, the peptide is widely expressed in the brain in which it functions as a neurotransmitter/neuromodulator influencing stressrelated behaviors and sympathetic output (1, 2).”
BackgroundDepressive symptoms are associated with reduced neutrophil function in hip fracture patients
Duggal, N. A., Upton, J., Phillips, A. C., Hampson, P., & Lord, J. M. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.07.004 · Cited by 39
“The hypothalamus–pituitary–adrenal (HPA) axis acts as a pivotal regulator of the stress responses by mobilising energy reserves and modulating immune responses (Tsigos and Chrousos, 2002).”
Cevik, R., Gur, A., Acar, S., Nas, K., & Sarac, A. J. (2004) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-5-47 · Cited by 39
“Moreover, decreased HPA axis activity was reported in some stress related states such as CFS, atypical and seasonal depression [35].”
BackgroundDelagneau, G., Twilhaar, E. S., Testa, R., van Veen, S., & Anderson, P. J. (2022) · Child Development · doi:10.1111/cdev.13885 · Cited by 43
“Stress and anxiety are also underpinned by similar biological reactions (e.g., activation of the hypothalamic– pituitary– adrenal axis and sympathetic nervous system; Graeff & Zangrossi Junior, 2010; Tsigos & Chrousos, 2002).”
BackgroundBashir, B., Alam, S., Khandale, N. B., Birla, D., Vishwas, S., Pandey, N. K., Gupta, G., Paudel, K. R., Dureja, H., Kumar, P., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102236 · Cited by 40
Noschang, C. G., Krolow, R., Pettenuzzo, L. F., Ávila, M. C., Fachin, A., Arcego, D. M., Toigo, E. V. P., Crema, L. M., Diehl, L. A., Vendite, D., et al. (2009) · Neurochemical Research · doi:10.1007/s11064-009-9945-4 · Cited by 39
“It is well known that chronic exposure to stress situations leads to a series of biochemical, physiological, and behavioral changes, thus, altering normal body homeostasis [ 17 ].”
BackgroundFilipčík, P., Novák, P., Mravec, B., Ondičová, K., Krajciova, G., Novák, M., & Květňanský, R. (2012) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-011-9788-9 · Cited by 38
Noschang, C. G., Pettenuzzo, L. F., Toigo, E. V. P., Andreazza, A. C., Krolow, R., Fachin, A., Ávila, M. C., Arcego, D. M., Crema, L. M., Diehl, L. A., et al. (2009) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2009.07.007 · Cited by 39
“The stress response leads to behavioral and metabolic changes in an effort to maintain body homeostasis and increase survival chances (Chrousos and Gold, 1992; Tsigos and Chrousos, 2002).”
BackgroundWester, V. L., Noppe, G., Savas, M., van den Akker, E. L. T., de Rijke, Y. B., & van Rossum, E. F. C. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.02.024 · Cited by 41
“Cortisol levels are usually measured in blood, saliva and urine (Nieman et al., 2008), but are highly variable due to the diurnal rhythm and the influence of acute stress (Tsigos and Chrousos, 2002).”
BackgroundSocial endocrinology: Hormones and social motivation
Mehta, P. H., & Josephs, R. A. (2011) · Cited by 39
Zhang, K., He, M.-Y., Wang, F., Zhang, H., Li, Y., Yang, J., & Wu, C. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00834 · Cited by 39
Acute Stress Assessment From Excess Cortisol Secretion: Fundamentals and Perspectives
Boucher, P., & Plusquellec, P. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00749 · Cited by 39
“By its physical properties (size and viscosity), glucocorticoids reach the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus and thus serve as feedback mediators that allow closed-loop regulation of the HPA axis (48, 49).”
BackgroundGuo, Y., Jiang, R., Su, A., Tian, H., Zhang, Y., Li, W., Tian, Y., Li, K., Sun, G., Han, R., et al. (2020) · Molecular Immunology · doi:10.1016/j.molimm.2020.06.004 · Cited by 39
Association between chronic low back pain and degree of stress: a nationwide cross-sectional study
Choi, S., Nah, S., Jang, H., Moon, J. E., & Han, S. (2021) · Scientific Reports · doi:10.1038/s41598-021-94001-1 · Cited by 53
Schaun, M. I., Dipp, T., Rossato, J. D. S., Wilhelm, E. N., Pinto, R. S., Rech, A., Plentz, R. D. M., de Bittencourt, P. I. H., & Reischak-Oliveira, Á. (2011) · Cell Biochemistry and Function · doi:10.1002/cbf.1781 · Cited by 39
Kokras, N., Sotiropoulos, I., Pitychoutis, P. M., Almeida, O. F. X., & Papadopoulou‐Daifoti, Z. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.07.077 · Cited by 39
Mazzotti, G. A., & Boere, V. (2009) · Laterality: Asymmetries of Body, Brain and Cognition · doi:10.1080/13576500802344420 · Cited by 37
“A large part of energy generation occurs by phosphorylation in muscle and neuronal cells, and part of this energy is spent as heat, increasing body temperature in several areas (Tsigos & Chrousos, 2002).”
BackgroundInfluentialAssociations of Psychological Distress with Metabolic Syndrome Among Japanese Urban Residents
Nishina, M., Nishina, K., Ohira, T., Makino, K., & Iso, H. (2011) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.6692 · Cited by 38
Repeated stress in combination with pyridostigmine
Lamproglou, I., Barbier, L., Diserbo, M., Fauvelle, F., Fauquette, W., & Amourette, C. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.08.031 · Cited by 38
Comorbidities of Chronic Urticaria: A glimpse into a complex relationship
Papapostolou, N., Xepapadaki, P. V., Katoulis, A., & Makris, M. P. (2022) · Frontiers in Allergy · doi:10.3389/falgy.2022.1008145 · Cited by 38
“Moreover, a causal relationship between stress and inflammatory disorders, including CU, has been reported (94, 95).”
BackgroundLiu, X., Yan, Z., Wang, T., Yang, X., Feng, F., Fan, L., & Jiang, J. P. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s84204 · Cited by 38
Duggal, N. A., Upton, J., Phillips, A. C., Hampson, P., & Lord, J. M. (2015) · AGE · doi:10.1007/s11357-015-9748-2 · Cited by 38
“A hallmark of the neuroendocrine immune response to stress is the activation of the hypothalamus-pituitaryadrenal (HPA) axis (Smith and Vale 2006) leading to increased circulating levels of immune suppressive glucocorticoids (Tsigos and Chrousos 2002).”
BackgroundStiller, A., Drugan, R. C., Hazi, A., & Kent, S. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.03.012 · Cited by 38
“Overall chronic stress tends to lead to immunosuppression (McEwen, 2000; Tsigos and Chrousos, 2002).”
Backgroundvan Gerven, D., Ferguson, T. D., & Skelton, R. W. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.05.003 · Cited by 43
“…hypothalamic–pituitary–a drenal (HPA) involves adrenocorticotropin-induced release of glucocorticoids (cortisol in humans, corticosterone in rats) (Tsigos & Chrousos, 2002) which in turn modulate brain activity in many areas, again including the hippocampus, caudate nucleus, and frontal lobes…”
Influences of the stress endocrine system on the reproductive endocrine axis in sheep (Ovis aries)
Narayan, E. J., & Parisella, S. (2017) · Italian Journal of Animal Science · doi:10.1080/1828051x.2017.1321972 · Cited by 37
Analysis of cortisol in dog hair - a potential biomarker of chronic stress: a review
Mesarčová, L., Kottferová, J., Skurková, L., Lešková, L., & Kmecová, N. G. (2017) · Veterinární Medicína · doi:10.17221/19/2017-vetmed · Cited by 44
“The stress response in vertebrates, mediated by the HPA axis, involves the release of adrenocorticotrophic hormone (ACTH) into the blood stream, which in turn acts on the adrenal cortex to activate the secretion of glucocorticoids (Tsigos and Chrousos 2002).”
BackgroundMigraine in young females with irritable bowel syndrome: still a challenge
Georgescu, D., Reisz, D., Gurban, C., Georgescu, L., Ioniță, I., Ancusa, O., & Lighezan, D. (2017) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s144955 · Cited by 38
Li, Y., Hou, S., Peng, W., Lin, Q., Chen, F., Yang, L., Li, F., & Huang, X. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/6919803 · Cited by 38
“Both external and internal biological changes such as diet, infection, and psychological events are well documented stressors for piglets, and concurrently, the secretion of cortisol could be escalated under such stressors [23].”
BackgroundThe effects of school‐based interventions on physiological stress in adolescents: A meta‐analysis
van Loon, A. W. G., Creemers, H. E., Okorn, A., Vogelaar, S., Miers, A. C., Saab, N., Westenberg, P. M., & Asscher, J. J. (2021) · Stress and Health · doi:10.1002/smi.3081 · Cited by 44
“…(i.e., the HPA axis), regulates the release of the hormone cortisol that influences many bodily functions, including the immune system, the body's metabolism, and the regulation of mood and emotions (Tsigos & Chrousos, 2002), necessary for responding to stressful situations (Nesse et al., 2016).”
BackgroundNwanaji-Enwerem, U., Condon, E. M., Conley, S., Wang, K., Iheanacho, T., & Redeker, N. S. (2022) · Sleep Health · doi:10.1016/j.sleh.2022.03.004 · Cited by 39
Cirillo, G., Negrete-Diaz, F., Yucumá, D., Virtuoso, A., Korai, S. A., Luca, C. D., Kaniušas, E., Papa, M., & Panetsos, F. (2022) · Cells · doi:10.3390/cells11244103 · Cited by 40
“CRF binds to specific receptors expressed by cells of the pituitary gland, releasing adrenocorticotropin, a hormone that modulates the cells in the zona fasciculata in the adrenal glands that, in turn, release glucocorticoids, which play a strong anti-inflammatory role [153,155,156].”
BackgroundHu, Y., Liu, P., Guo, D., Rahman, K., Wang, D., & Xie, T. (2010) · Pharmaceutical Biology · doi:10.3109/13880200903280034 · Cited by 38
“…(HPA) axis characterized by hypersecretion of corticotrophin-releasing factor (CRF), which stimulates adrenocorticotrophic hormone (ACTH) release (Tsigos & Chrousos, 2002; Barden, 2004), and thus elevates serum corticosterone (CORT) levels in depressive disorders (O’Brien et al., 2004).”
BackgroundAndersen, B. L., Golden‐Kreutz, D. M., Emery, C. F., & Thiel, D. L. (2009) · Cognitive and Behavioral Practice · doi:10.1016/j.cbpra.2008.11.002 · Cited by 40
“The release of corticotrophin-releasing hormone (CRH), a main component of the stress system, may suppress appetite (Tsigos & Chrousos, 2002).”
BackgroundHampl, R., Stárka, L., & Janský, L. (2006) · Physiological Research · doi:10.33549/physiolres.930758 · Cited by 38
Calle, M., Kozicz, T., van der Linden, E., Desfeux, A., Veening, J. G., Barendregt, H. P., & Roubos, E. W. (2006) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2006.01.007 · Cited by 38
“Corticotropin-releasing factor (CRF) is a 41 amino acid neuropeptide that in mammals controls a wide range of physiological responses to physical and emotional stressors (e.g., Tsigos and Chrousos, 2002; Vale et al., 1981), including neuroendocrine and behavioral * Corresponding author.”
BackgroundKurhaluk, N., Kołodziejska, R., Kamiński, P., & Ткаченко, Г. М. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262311706 · Cited by 43
Jahagirdar, V., & McNay, E. C. (2012) · Metabolic Brain Disease · doi:10.1007/s11011-012-9291-0 · Cited by 37
“Glucocorticoid treatment lowers TH levels by suppressing TSH secretion, as well as via immuno-suppressive properties that may aid in controlling autoimmune processes in conditions like Graves' Disease (Chrousos 1995; Tsigos and Chrousos 2002).”
Nuclear receptors in transgenerational epigenetic inheritance
Ozgyin, L., Erdős, E., Bojcsuk, D., & Bálint, B. L. (2015) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2015.02.012 · Cited by 37
Thoma, M. V., Gianferante, D., Hanlin, L. C., Fiksdal, A. S., Chen, X., & Rohleder, N. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.11.030 · Cited by 40
“Within minutes, the HPA axis is activated and releases its main effector, the glucocorticoid hormone cortisol, to further increase available energy (del Rey et al., 2008; Jacobson, 2005; Sapolsky et al., 2000; Tsigos and Chrousos, 2002).”
BackgroundMeakin, C. J., Martin, E. M., Junior, H. P. D. O. S., Mokrova, I. L., Kuban, K., O’Shea, T. M., Joseph, R. M., Smeester, L., & Fry, R. C. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2018.02.007 · Cited by 37
“The neuroendocrine system serves as an interface between the brain and many of the peripheral endocrine systems and is integral for maintaining homeostasis throughout the body (Tsigos and Chrousos, 2002).”
Chen, L., Qi, X., & Zheng, J. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00588 · Cited by 38
Lorentz, K. O., Lemmers, S. A. M., Chrysostomou, C., Dirks, W., Zaruri, M. R., Foruzanfar, F., & Sajjadi, S. M. S. (2019) · Journal of Archaeological Science · doi:10.1016/j.jas.2019.01.007 · Cited by 37
Peterson, L. M., Stock, M. L., Monroe, J., Molloy-Paolillo, B. K., & Lambert, S. F. (2020) · The Journal of Social Psychology · doi:10.1080/00224545.2020.1729685 · Cited by 40
“The acute cortisol stress-response influences cardiovascular, inflammatory, and immune physiological responses to efficiently react to an immediate stressor (Mills & Ziegler, 2008; Tsigos & Chrousos, 2002).”
BackgroundCorticotropin-releasing factor-binding protein, stress and major depression
Eede, F. V. D., Broeckhoven, C. V., & Claes, S. J. (2005) · Ageing Research Reviews · doi:10.1016/j.arr.2005.02.002 · Cited by 37
Lymphocyte reduction induced by hindlimb unloading: distinct mechanisms in the spleen and thymus
Li Xin, W. E. I., Zhou, J., Roberts, A. I., & Shi, Y. (2003) · Cell Research · doi:10.1038/sj.cr.7290189 · Cited by 37
Etiopathogenetic mechanisms of fibromyalgia syndrome
Stisi, S., Cazzola, M., Buskila, D., Späth, M., Giamberardino, M. A., Sarzi‐Puttini, P., Arioli, G., Alciati, A., Leardini, G., Gorla, R., et al. (2011) · Reumatismo · doi:10.4081/reumatismo.2008.1s.25 · Cited by 37
“The hypothalamic-pituitary-adrenal axis (HPA-axis) FMS patients have been shown to present with HPA axis alterations (76-80).”
BackgroundNeu, M., Matthews, E. E., King, N. A., Cook, P. F., & Laudenslager, M. L. (2014) · Journal of Pediatric Oncology Nursing · doi:10.1177/1043454213520346 · Cited by 37
“The hypothalamic-pituitary-adrenal axis (HPA) is the part of the endocrine system that regulates responses to physical and mental stress to facilitate the maintenance of physiologic homeostasis (Tsigos & Chrousos, 2002).”
BackgroundFamily environment is associated with HPA-axis activity in adolescents. The TRAILS study
Marsman, R., Nederhof, E., Rosmalen, J. G. M., Oldehinkel, A. J., Ormel, J., & Buitelaar, J. K. (2011) · Biological Psychology · doi:10.1016/j.biopsycho.2011.12.013 · Cited by 41
“Boyce, W.T., Ellis, B.J., 2005.”
BackgroundInfluentialFerri, C. C., Yuill, E. A., & Ferguson, A. V. (2005) · Regulatory Peptides · doi:10.1016/j.regpep.2005.01.004 · Cited by 37
The role of estrogen in intrusive memories
Cheung, J., Chervonsky, L., Felmingham, K. L., & Bryant, R. A. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.07.005 · Cited by 36
“The slower-acting HPA system involves the production of cortisol by the adrenal cortex, which increases blood sugar levels and metabolism (Tsigos & Chrousos, 2002).”
BackgroundStress, depression, and hippocampus: from biochemistry to electrophysiology
Idunkova, A., Lacinová, Ľ., & Hoppanová, L. (2023) · General Physiology and Biophysics · doi:10.4149/gpb_2023001 · Cited by 36
The critical role of gut-brain axis microbiome in mental disorders
Basiji, K., Sendani, A. A., Ghavami, S. B., Farmani, M., Kazemifard, N., Sadeghi, A., Lotfali, E., & Aghdaei, H. A. (2023) · Metabolic Brain Disease · doi:10.1007/s11011-023-01248-w · Cited by 37
Gelfo, F., Tirassa, P., Bartolo, P. D., Croce, N., Bernardini, S., Caltagirone, C., Petrosini, L., & Angelucci, F. (2012) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2012.00314.x · Cited by 36
“According to these studies, NPY may exert its anxiolytic and antidepressant action by antagonizing the hypothalamic–pituitary–adrenal (HPA) axis [10–13] which is chronically hyperactivated in stress-related disorders [2,14].”
BackgroundThinking of attachments reduces noradrenergic stress response
Bryant, R. A., & Chan, L. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.06.004 · Cited by 40
“arousal) (Tsigos and Chrousos, 2002).”
Hutmacher, F. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.539799 · Cited by 55
Mazurek, B., Stöver, T., Haupt, H., Klapp, B. F., Adli, M., Gross, J. P., & Szczepek, A. J. (2009) · HNO · doi:10.1007/s00106-009-2001-5 · Cited by 38
Bulimia nervosa—a primary defect in the hypthalamic–pituitary–adrenal axis?
Birketvedt, G. S., Drivenes, E., Agledahl, I., Sundsfjord, J., Olstad, R., & Florholmen, J. R. (2006) · Appetite · doi:10.1016/j.appet.2005.11.007 · Cited by 36
Silva, S. M., & Madeira, M. D. (2012) · Brain Research · doi:10.1016/j.brainres.2012.01.013 · Cited by 36
“…HPA axis by increasing the synthesis of CRH and VP in the parvocellular neurons of the PVN and the release of ACTH by the pituitary, leading to the production of glucocorticoids (Harbuz and Lightman, 1992; Itoi et al., 2004; Kovács and Sawchenko, 1996; Ma et al., 1997; Tsigos and Chrousos, 2002).”
BackgroundBiological Bases of the Stress Response
Kudielka, B. M., & Kirschbaum, C. (2007) · Elsevier eBooks · doi:10.1016/b978-012370632-4/50004-8 · Cited by 37
Walf, A. A., & Frye, C. A. (2003) · Behavioural Brain Research · doi:10.1016/s0166-4328(03)00067-6 · Cited by 36
Perceived stress in women with recurrent vulvovaginal candidiasis
Ehrström, S., Kornfeld, D., & Rylander, E. (2007) · Journal of Psychosomatic Obstetrics & Gynecology · doi:10.1080/01674820601168176 · Cited by 36
“A constantly activated hypothalamus-pituitary-adrenal axis will impair the innate part of the immune system, which is involved in mucosal infection and inflammation [12,14,15].”
BackgroundLiu, X., Wellman, L. L., Yang, L., Ambrozewicz, M. A., Tang, X., & Sanford, L. D. (2011) · Sleep · doi:10.5665/sleep.1394 · Cited by 35
Modelling female physiology from head to Toe: impact of sex hormones, menstrual cycle, and pregnancy
Abo, S., Smith, D., Stadt, M., & Layton, A. (2022) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2022.111074 · Cited by 35
Kotkowska, Z., & Strzelecki, D. (2022) · Pharmaceuticals · doi:10.3390/ph15040391 · Cited by 66
“Chronically high GC levels induce receptor resistance to GC, subsequently causing further increase in their secretion and disturbances in the functioning of the hypothalamic–pituitary–adrenal axis, increasing the susceptibility to autoimmune processes and depression [22,23].”
BackgroundThe Wistar Kyoto Rat: A Model of Depression Traits
Redei, E. E., Udell, M. E., Woods, L. C. S., & Chen, H. (2022) · Current Neuropharmacology · doi:10.2174/1570159x21666221129120902 · Cited by 37
“In chronic stress, sustained elevations in cortisol have deleterious effects on the organism [72, 73].”
BackgroundLatent state trait modeling of children's cortisol at two points of the diurnal cycle
Kertes, D. A., & van Dulmen, M. H. M. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.06.009 · Cited by 35
“Circulating levels of cortisol, the end product of the HPA axis in humans, follows a diurnal rhythm typically characterized by high levels in the early morning, including a burst of activity characterized by a rapid rise and decline known as the awakening response, and a nadir near sleep onset (Pruessner et al., 1997;…”
Metadata
- Authors
- Tsigos, C., & Chrousos, G. P.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- National Institutes of Health (US)
- Corresponding author
- Chrousos, George P
- ORCID
- Chrousos, George P
- Venue
- Journal of Psychosomatic Research
- Publisher
- Elsevier BV
- Published
- 2002-10
- Volume
- 53
- Issue
- 4
- Pages
- 865-871
- ISSN
- 0022-3999 (ISSN-L)
- OpenAlex
- W1971639265
- Cited by
- 2,822
- References
- 49
- Citations by year
- 2026: 86 · 2025: 126 · 2024: 153 · 2023: 137 · 2022: 143 · 2021: 180 · 2020: 150 · 2019: 130 · 2018: 150 · 2017: 162 · 2016: 149 · 2015: 146 · 2014: 142 · 2013: 145 · 2012: 130
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychosomatic Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- H, hypothalamic-pituitary-adrenal axis, stress response, locus coeruleus-norepinephrine system, beta-endorphin, glucocorticoids, catecholamines, amygdala, hippocampus, somatostatin, insulin resistance, metabolic syndrome X, bone loss, osteoporosis
- MeSH terms
- Autonomic Nervous System, Corticotropin-Releasing Hormone, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Stress, Physiological, Feedback, Physiological
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
