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Hypothalamic-pituitary-adrenal (HPA) axis

Published: Jul 17, 2023
  /  
Updated: Jul 27, 2023

Written by Oseh Mathias

Founder, SpeechFit

The Hypothalamic-Pituitary-Adrenal (HPA) axis is a complex set of direct influences and feedback interactions among three endocrine glands: the hypothalamus, the pituitary gland, and the adrenal glands[1]. It is a major neuroendocrine system that controls reactions to stress and regulates many body processes, including digestion, the immune system, mood and emotions, sexuality, and energy storage and expenditure[2].

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Diagram of the HPA axis. Sweis, B. M. (2016).[3]

It is the mechanism for a set of interactions among glands, hormones, and parts of the midbrain that mediate the general adaptation syndrome (GAS)[4]. The HPA axis involves the release of corticotropin-releasing hormone (CRH) from the hypothalamus, which stimulates the release of adrenocorticotropic hormone (ACTH) from the pituitary[5]. ACTH then stimulates the release of cortisol from the adrenal cortex[6].

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HPA axis modulation of glucocorticoids. Burford, N. G., Webster, N. A., & Cruz-Topete, D. (2017)[7]

Cortisol, a glucocorticoid, mobilizes nutrients, modifies the body's response to inflammation, stimulates the liver to raise the blood sugar, and also helps to control the amount of water in the body[8]. Cortisol release is also a method through which the body mobilizes energy to fight off or retreat from danger, which is why it is often referred to as a "stress hormone"[9].

The HPA axis works in a rhythmic fashion, with levels of cortisol in the blood typically highest in the early morning and lowest around midnight, although stress and certain diseases can disrupt this rhythm[10].

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Circadian rhythm of the HPA axis. Torpy, D. J., & Saranapala, M. (2015).[11]

Feedback inhibition on the HPA axis occurs when elevated levels of glucocorticoids signal the hypothalamus and pituitary to reduce output of CRH and ACTH, respectively[12]. This intricate system allows the body to maintain homeostasis and respond to stress in a balanced way[13].

Author

Oseh Mathias

SpeechFit Founder

Oseh is a software engineer, entrepreneur and founder of SpeechFit. Oseh is passionate about improving health and wellbeing outcomes for neurodiverse people and healthcare providers alike.

References

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  • 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.

  • Sweis, B. M. (2016). Basic hypothalamic–pituitary–adrenal axis summary [PNG diagram]. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:HPA_Axis_Diagram_(Brian_M_Sweis_2012).svg

  • Kudielka, B. M., & Kirschbaum, C. (2005). Sex differences in HPA axis responses to stress: a review. Biological psychology, 69(1), 113-132.

  • Smith, S. M., & Vale, W. W. (2006). The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues in clinical neuroscience, 8(4), 383.

  • Stavreva, D. A., Wiench, M., John, S., Conway-Campbell, B. L., McKenna, M. A., Pooley, J. R., ... & Hager, G. L. (2009). Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription. Nature cell biology, 11(9), 1093-1102.

  • Burford, N. G., Webster, N. A., & Cruz-Topete, D. (2017). Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System [Image in the article "Int. J. Mol. Sci. 2017, 18(10), 2150"]. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms18102150

  • Cohen, S., Janicki-Deverts, D., Doyle, W. J., Miller, G. E., Frank, E., Rabin, B. S., & Turner, R. B. (2012). Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proceedings of the National Academy of Sciences, 109(16), 5995-5999.

  • Fries, E., Dettenborn, L., & Kirschbaum, C. (2009). The cortisol awakening response (CAR): facts and future directions. International Journal of Psychophysiology, 72(1), 67-73.

  • Dickmeis, T. (2009). Glucocorticoids and the circadian clock. Journal of endocrinology, 200(1), 3-22.

  • Torpy, D. J., & Saranapala, M. (2015). Circadian rhythm of the hypothalamic-pituitary-adrenal (HPA) axis [Figure 1 in the article "Cushing's syndrome vs simple obesity. How can a needle be found in the haystack?"]. ResearchGate. https://www.researchgate.net/figure/Circadian-rhythm-of-the-hypothalamic-pituitary-adrenal-HPA-axis-Cortisol-levels-rise_fig2_272819802

  • Ronchi, C. L., Varlamov, E. V., & Wass, J. A. (2013). Corticotropin-releasing hormone (CRH) stimulation tests in patients with hypothalamic–pituitary–adrenal disease: a review. Clinical endocrinology, 78(6), 803-810.

  • Nicolaides, N. C., Kyratzi, E., Lamprokostopoulou, A., Chrousos, G. P., & Charmandari, E. (2015). Stress, the stress system and the role of glucocorticoids. Neuroimmunomodulation, 22(1-2), 6-19.