Log InSign Up
G
4 min read

Glucocorticoids

Published: Jul 17, 2023
  /  
Updated: Jul 26, 2023

Written by Oseh Mathias

Founder, SpeechFit

Glucocorticoids are a class of steroid hormones that are produced and released by the adrenal glands, which are located on top of the kidneys [1]. The main glucocorticoid in humans is cortisol, also known as hydrocortisone [2].

image within the content - in line image
Chemical structure of cortisol, the most common glucocorticoid.

Glucocorticoids are released from the adrenal cortex in response to stress and low blood glucose levels [3].

image within the content - in line image
Adrenal gland showing the adrenal medulla and adrenal cortex. Cleveland Clinic. (2022)[4].

This is a part of the body's "fight or flight" response system and is regulated by a process known as the hypothalamic-pituitary-adrenal (HPA) axis [5].

Here's a step-by-step description of the process:

  1. The process begins in the hypothalamus, a region of the brain that serves as the body's main control center for stress responses. In response to stress or low blood glucose, the hypothalamus releases corticotropin-releasing hormone (CRH) [6].

  2. CRH then travels to the pituitary gland, another part of the brain. In response to the presence of CRH, the pituitary gland produces and releases adrenocorticotropic hormone (ACTH) [7].

  3. ACTH is transported through the bloodstream to the adrenal glands, which are small, triangle-shaped glands located on top of the kidneys [8].

  4. Upon receiving ACTH, the adrenal glands secrete glucocorticoids, like cortisol, into the bloodstream [9]. The primary role of cortisol is to increase the amount of glucose in the bloodstream, helping the body to mobilise resources and respond to stress [10].

  5. Increased cortisol levels in the blood have a negative feedback effect on the hypothalamus and pituitary gland. This means that when enough cortisol has been released, the hypothalamus and pituitary gland are signalled to stop producing CRH and ACTH, which in turn stops the adrenal glands from producing more cortisol [11]. This ensures that the body doesn't produce too much cortisol and helps maintain a balance in the body's systems [12].

  6. Finally, once the stressor is removed or the body's glucose levels return to normal, the system returns to its baseline state, and cortisol levels decrease [13].

This process allows the body to respond quickly and effectively to stressful situations, providing the energy necessary to react to the immediate concern [14].

image within the content - in line image
The hypothalamic-pituitary-adrenal (HPA) axis. Timmermans, S., Souffriau, J., & Libert, C. (2019)[15]

Once glucocorticoids like cortisol are released into the bloodstream, they have fairly rapid effects on the body [16]. The exact timing can depend on various factors, such as the individual's overall health, the specific stressor, and other hormonal or physiological conditions [17]. However, generally, the physiological effects of cortisol can start to be felt within minutes of its release [18].

Here are some primary functions of glucocorticoids:

  • Metabolism Regulation: Glucocorticoids, like cortisol, help maintain blood glucose levels, and they play a crucial role in fat, protein, and carbohydrate metabolism [19]. They stimulate gluconeogenesis (the production of glucose), which can provide the body with energy, especially during periods of fasting or stress [20].

  • Immune Response: Glucocorticoids have potent anti-inflammatory and immunosuppressive properties [21]. They limit the body's immune response to prevent overreaction and help control inflammation [22]. This is why synthetic glucocorticoids are often used to treat autoimmune diseases and inflammatory conditions [23].

  • Stress Response: Glucocorticoids are key components of the body's "fight or flight" response [24]. In response to stress, they help prepare the body to handle the perceived threat by increasing blood sugar levels, suppressing non-emergency bodily functions (like digestion and immune response), and enhancing the body's metabolism of glucose to provide quick energy [25].

  • Central Nervous System Effects: Glucocorticoids can affect mood, cognition, and behavior [26]. They play a role in memory consolidation, particularly for emotionally loaded memories [27].

  • Cardiovascular Function: Glucocorticoids help maintain blood pressure by increasing the sensitivity of blood vessels to other hormones (like epinephrine and norepinephrine) that cause vasoconstriction [28].

  • Bone Metabolism: They can influence the body's calcium absorption and bone remodelling [29]. However, prolonged exposure to glucocorticoids can lead to bone loss and increase the risk of fractures [30].

  • Development and Growth: Glucocorticoids play a critical role in fetal development, including the maturation of the lungs [31][32].

While glucocorticoids have essential physiological functions, prolonged exposure to high levels of glucocorticoids or the chronic use of synthetic glucocorticoid medications can have adverse effects on health, including suppression of the immune system, bone loss, muscle wasting, weight gain, and mood changes [33].

Cortisol, the primary glucocorticoid, is just one of several hormones within the glucocorticoid class. Other examples of glucocorticoids include cortisone and prednisone, which are often used as therapeutic medications to mimic the effects of cortisol in managing various medical conditions.


Author

Oseh Mathias

SpeechFit Founder

Oseh is passionate about improving health and wellbeing outcomes for neurodiverse people and healthcare providers alike.


References
  • Silverman, M. N., & Sternberg, E. M. (2012). Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction. Annals of the New York Academy of Sciences, 1261(1), 55–63. https://doi.org/10.1111/j.1749-6632.2012.06633.x

  • Pariante, C. M. (2017). Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation. European Neuropsychopharmacology, 27(6), 554–559. https://doi.org/10.1016/j.euroneuro.2017.04.001

  • Kadmiel, M., & Cidlowski, J. A. (2013). Glucocorticoid receptor signaling in health and disease. Trends in Pharmacological Sciences, 34(9), 518–530. https://doi.org/10.1016/j.tips.2013.07.003

  • Cleveland Clinic. (2022). Adrenal Gland. Retrieved July 26, 2023, from https://my.clevelandclinic.org/health/body/23005-adrenal-gland

  • Chrousos, G. P. (2009). Stress and disorders of the stress system. Nature Reviews Endocrinology, 5(7), 374–381. https://doi.org/10.1038/nrendo.2009.106

  • Charmandari, E., Tsigos, C., & Chrousos, G. (2005). Endocrinology of the stress response. Annual review of physiology, 67, 259-284. https://doi.org/10.1146/annurev.physiol.67.040403.120816

  • Tsigos, C., & Chrousos, G. P. (2002). Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. Journal of Psychosomatic Research, 53(4), 865–871. https://doi.org/10.1016/S0022-3999(02)00429-4

  • Herman, J. P., McKlveen, J. M., Ghosal, S., Kopp, B., Wulsin, A., Makinson, R., ... & Myers, B. (2016). Regulation of the hypothalamic-pituitary-adrenocortical stress response. Comprehensive Physiology, 6(2), 603-621. https://doi.org/10.1002/cphy.c150015

  • Katsu, Y., & Iguchi, T. (2016). Subchapter 84B – Glucocorticoid Receptors and Their Role in Regulating the Stress Response. In K. W. Jeon (Ed.), International Review of Cell and Molecular Biology (Vol. 321, pp. 195–234). https://doi.org/10.1016/bs.ircmb.2015.09.009

  • Cadegiani, F. A., & Kater, C. E. (2020). Hormonal aspects of overtraining syndrome: a systematic review. BMC sports science, medicine and rehabilitation, 12, 30. https://doi.org/10.1186/s13102-020-00170-w

  • Zannas, A. S., & Chrousos, G. P. (2017). Epigenetic programming by stress and glucocorticoids along the human lifespan. Molecular psychiatry, 22(5), 640-646. https://doi.org/10.1038/mp.2017.35

  • Chrousos, G. P. (2015). Stress and sex versus immunity and inflammation. Science signaling, 8(399), fs10-fs10. https://doi.org/10.1126/scisignal.aad4049

  • Dedovic, K., Duchesne, A., Andrews, J., Engert, V., & Pruessner, J. C. (2009). The brain and the stress axis: the neural correlates of cortisol regulation in response to stress. NeuroImage, 47(3), 864-871. https://doi.org/10.1016/j.neuroimage.2009.05.074

  • Ulrich-Lai, Y. M., & Herman, J. P. (2009). Neural regulation of endocrine and autonomic stress responses. Nature Reviews Neuroscience, 10(6), 397–409. https://doi.org/10.1038/nrn2647

  • Timmermans, S., Souffriau, J., & Libert, C. (2019). A General Introduction to Glucocorticoid Biology. Frontiers in Immunology, 10. Figure 1, Hypothalamic-pituitary-adrenal axis. https://doi.org/10.3389/fimmu.2019.01545

  • Miller, G. E., Chen, E., & Zhou, E. S. (2007). If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. Psychological Bulletin, 133(1), 25–45. https://doi.org/10.1037/0033-2909.133.1.25

  • Stavreva, D. A., & Hager, G. L. (2015). Chromatin structure and gene regulation in the immune system. Annual Review of Immunology, 33, 539-568. https://doi.org/10.1146/annurev-immunol-032713-120147

  • Joëls, M., & Baram, T. Z. (2009). The neuro-symphony of stress. Nature Reviews Neuroscience, 10(6), 459–466. https://doi.org/10.1038/nrn2632

  • Lightman, S. L. (2008). The neuroendocrinology of stress: a never ending story. Journal of neuroendocrinology, 20(6), 880-884. https://doi.org/10.1111/j.1365-2826.2008.01711.x

  • Rhen, T., & Cidlowski, J. A. (2005). Antiinflammatory action of glucocorticoids—new mechanisms for old drugs. New England Journal of Medicine, 353(16), 1711–1723. https://doi.org/10.1056/NEJMra050541

  • Coutinho, A. E., & Chapman, K. E. (2011). The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Molecular and Cellular Endocrinology, 335(1), 2-13. https://doi.org/10.1016/j.mce.2010.04.005

  • Sapolsky, R. M., Romero, L. M., & Munck, A. U. (2000). How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocrine reviews, 21(1), 55-89. https://doi.org/10.1210/er.21.1.55

  • Busillo, J. M., & Cidlowski, J. A. (2013). The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore. Trends in Endocrinology & Metabolism, 24(3), 109-119. https://doi.org/10.1016/j.tem.2012.11.005

  • Joëls, M., Sarabdjitsingh, R. A., & Karst, H. (2012). Unraveling the time domains of corticosteroid hormone influences on brain activity: rapid, slow, and chronic modes. Pharmacological reviews, 64(4), 901-938. https://doi.org/10.1124/pr.112.005892

  • Groeneweg, F. L., Karst, H., de Kloet, E. R., & Joëls, M. (2011). Rapid non-genomic effects of corticosteroids and their role in the central stress response. Journal of Endocrinology, 209(2), 153-167. https://doi.org/10.1530/JOE-10-0472

  • McEwen, B. S., & Morrison, J. H. (2013). The brain on stress: vulnerability and plasticity of the prefrontal cortex over the life course. Neuron, 79(1), 16-29. https://doi.org/10.1016/j.neuron.2013.06.028

  • Roozendaal, B., McEwen, B. S., & Chattarji, S. (2009). Stress, memory and the amygdala. Nature Reviews Neuroscience, 10(6), 423–433. https://doi.org/10.1038/nrn2651

  • Sapolsky, R. M. (1992). Cortisol concentrations and the social significance of rank instability among wild baboons. Psychoneuroendocrinology, 17(6), 701-709. https://doi.org/10.1016/0306-4530(92)90029-7

  • Hardy, R. S., Zhou, H., Seibel, M. J., & Cooper, M. S. (2018). Glucocorticoids and bone: consequences of endogenous and exogenous excess and replacement therapy. Endocrine Reviews, 39(5), 519-548. https://doi.org/10.1210/er.2018-00084

  • Canalis, E., Mazziotti, G., Giustina, A., & Bilezikian, J. P. (2007). Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporosis international, 18(10), 1319-1328. https://doi.org/10.1007/s00198-007-0394-0

  • Matthews, S. G., & McGowan, P. O. (2019). Developmental programming of the HPA axis and related behaviours: epigenetic mechanisms. Journal of Endocrinology, 242(1), T69-T79. https://doi.org/10.1530/JOE-19-0064

  • Smith, R. E., & Maguire, J. A. (2004). Development of fetal hypothalamic-pituitary-adrenal axis. Seminars in neonatology, 9(4), 281-289. https://doi.org/10.1016/j.siny.2004.01.012

  • Fardet, L., Flahault, A., Kettaneh, A., Tiev, K. P., Généreau, T., Tolédano, C., Lebbé, C., & Cabane, J. (2007). Corticosteroid-induced clinical adverse events: frequency, risk factors and patient's opinion. British Journal of Dermatology, 157(1), 142-148. https://doi.org/10.1111/j.1365-2133.2007.07907.x