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What Is the Hypothalamic-Pituitary-Adrenal Axis?

An adrenal gland on top of a kidney.
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  • Written By: Solomon Branch
  • Edited By: A. Joseph
  • Last Modified Date: 19 August 2014
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The hypothalamic-pituitary-adrenal (HPA) axis is a set of actions and feedback responses between the hypothalamus and the pituitary and adrenal glands. The HPA axis assists in regulating temperature, digestion, immune system, mood, sexuality and overall energy. It also has a large part in controlling reactions to stress, either physical or mental.

The hypothalamus and pituitary gland are located in the brain; the adrenals sit atop the kidneys. The hypothalamus controls hunger, fatigue, sleep and body temperature, and it secretes hormones. It has a close relationship with the pituitary gland, because the hormones that it secretes stimulate or inhibit the pituitary gland to secrete its hormones, which also control the body’s functions. The adrenal glands, besides regulating the function of the kidneys, also release hormones that are part of the stress response.

The function of the hypothalamic-pituitary-adrenal axis is complex and has many functions, but most of them relate to regulating the effects of stress on the functions of body. The first step in this process occurs in the hypothalamus, which releases a hormone called corticotrophin-releasing factor (CRF) in reaction to stress. CRF hormones then stimulate the pituitary gland, which then releases adrenocorticotropic hormone (ACTH). In turn, ACTH stimulates the adrenal gland that releases cortisol. Cortisol is responsible for, among other things, slowing the immune system's inflammatory response and controlling blood pressure.

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The hypothalamic-pituitary-adrenal axis keeps things in balance through a positive and negative feedback system. It is dependent on the amount of cortisol in the blood, stress level and the wake/sleep cycle. If, for instance, the cortisol level gets too high, the hypothalamus and pituitary gland are stimulated and decrease their production of the hormones that began the process, thereby keeping the body in balance. Constant stress of any kind can lead to dysfunction of the HPA axis.

Many of the problems with which the HPA axis is involved are mood disorders, such as anxiety disorder, bipolar disorder and insomnia. It also is a factor in chronic fatigue syndrome, fibromyalgia and burnout. Constant stress of the hypothalamic-pituitary-adrenal axis can also be a contributing factor to irritable bowel syndrome and alcoholism. Many of the mood disorders are treated with anti-depressants, which function by regulating the hypothalamic-pituitary-adrenal axis.

Much research has been done on the HPA axis and its relation to stress, both physical and mental. One of the interesting things to note about the research is that it can be performed on many different animals, not just humans. The hypothalamic-pituitary-adrenal axis is actually common to all mammals as well as some other vertebrates.

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