What Is the Hypothalamic-Pituitary-Adrenal (HPA) Axis?

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The hypothalamic-pituitary-adrenal (HPA) axis is a vital body system. The parts of the HPA axis include the hypothalamus, the pituitary gland, and the adrenal glands.

The HPA axis is connected to the central nervous system and the endocrine system. Together they work to adjust the balance of hormones in the body and affect the stress response. The stress response is how the body reacts to a stressful event, which can include raising the heart rate or sweating.

This article will discuss the structure of the HPA axis, how it works, its functions in the body, its significance, and associated conditions.

A person sitting on a couch looking stressed

Nicola Katie / Getty Images


The HPA axis is made up of the hypothalamus, the pituitary gland, and the adrenal glands. Hormones play an important role in the HPA axis. Hormones are chemicals in the body that act like messengers. They give various body systems orders to start or stop different functions. 

The hypothalamus is a small structure in the brain. It is located at the center of the base of the brain, near the pituitary gland, and is about the size of a walnut. The hypothalamus is important in regulating hormone levels in the body. It also plays a role in regulating many body systems including the sleep/wake cycle, body temperature, and weight.

The pituitary gland is about the size of a pea and is located at the base of the brain. Its role is to create and release hormones in the body. Hormones are vital in many body functions, including those that affect growth and maturation.

The hormones that the pituitary produces which are important in the HPA axis include:

  • Adrenocorticotropic hormone: A hormone that causes the adrenal glands to release cortisol, which is involved in the stress response
  • Corticotropin-releasing factor: A messenger hormone that tells the pituitary gland to release adrenocorticotropic hormone

The adrenal glands are found in the abdomen, on either side of the body, above the kidneys. They are responsible for producing several types of hormones, including cortisol, aldosterone, adrenaline, and noradrenaline.

Graphic shows how the stress response system works starting with the hypothalamus and ending with cortisol release.

ttsz / Getty Images

How It Works

When the body experiences some kind of stress, the HPA axis may get activated. It sets off a series of events in the body in response. Stress can mean not only emotional stress but also being scared or nervous. The HPA axis gets the message and goes to work in seconds.

The hypothalamus then releases corticotropin-releasing hormone. That activates a part of the nervous system (called the sympathetic nervous system), which reacts by increasing heart rate and sweating, for example.

In addition to those physical changes, corticotropin-releasing hormone also affects the pituitary gland. It tells the pituitary gland to start releasing adrenocorticotropic hormone.

The adrenocorticotropic hormone is released into the bloodstream. Through the blood, it makes its way to the adrenal glands in the abdomen. It binds to a spot on the adrenal glands. The adrenal glands then get the message that they should start producing cortisol and other substances. 


The result of the activation of the HPA axis is the release of cortisol. Cortisol is a steroidal hormone. It has many effects and is sometimes called the “stress hormone.” Cortisol must be balanced in the body: too much or too little can have wide-ranging health effects.

Cortisol has many properties that help a body respond to a stressful event. It sends more blood to muscles, increases the amount of glucose in the blood, and increases blood pressure.

These are all helpful responses during a stressful event that might be a “fight or flight” situation. That is how we define a situation where there may be a need to defend oneself or run away from a harmful event.

Cortisol also turns off or dials down those body functions that won’t help in a stressful situation. 

There is another part to the HPA axis, called the negative feedback loop. Cortisol isn't supposed to be produced for long periods of time. Its production should end when the stressful event is over.

For that reason, the cortisol produced by the stress response also turns around and acts upon the hypothalamus and the pituitary gland. It connects with receptors on the hypothalamus. This causes the HPA axis to slow down and stop the production of corticotropin-releasing and adrenocorticotropic hormones.


The activation of the HPA axis is an important body function. However, when it is over activated, there could be health problems. Learning more about how the HPA axis controls the release of cortisol and its effects on the body may help better understand the stress response.

Exposure to stress, either for short periods regularly or for long periods, can negatively affect people’s quality of life. As the HPA axis is better studied, it could lead to more effective treatments for stress, anxiety, and other conditions that occur with high cortisol levels.

Associated Conditions

Your body needs to respond quickly to stress in our environment. For example: if there is a tree falling near you, you need to be able to get out of the way in a hurry. The stress response, which includes increased heart rate and extra energy, can help keep you safe.

However, stress can also be chronic, going on for long periods, such as during a pandemic or after the death of a loved one. Long periods of stress can cause the HPA axis to go into effect too often and release too much cortisol.

While higher cortisol levels are needed at certain times, they can be harmful when elevated for too long. This is because cortisol may suppress the immune system. If that dampening continues, the person could be more susceptible to infections.

Higher levels of cortisol over long periods may also affect memory. Chronic stress and the release of cortisol could cause problems with memory and attention.

Some of the other conditions that can occur with too much cortisol in the body include:

  • Diabetes: A disease that affects the body’s ability to regulate blood sugar levels
  • Dyslipidemia: Having lipid levels in the blood that are out of the normal range
  • Hypertension: High blood pressure which could lead to complications, such as heart disease
  • Neurodegeneration: Damage to nerve cells in the body, which can have many effects on the body
  • Osteoporosis: A condition that causes bones to become thinner and break more easily


The hypothalamic-pituitary-adrenal (HPA) axis involves the central nervous system and the endocrine system adjusting the balance of hormones in response to stress. Stress results in the hypothalamus stimulating the pituitary gland to release hormones that further cause the adrenal glands to release cortisol.

Cortisol prepares the body for "fight or flight." High levels of cortisol signal the hypothalamus that it no longer needs to stimulate the pituitary gland to raise levels further. Long periods of stress leading to chronically high cortisol may suppress the immune system and increase the risk for several conditions.

A Word From Verywell

The human body has systems such as the HPA axis that help you avoid dangerous events. But many people have chronic stress that may upset the balance this system is meant to maintain. If you feel you need help, there are many stress management techniques you can employ. A mental health professional may also be able to guide you to solutions.

3 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. National Institutes of Health. About adrenal gland disorders

  2. Bellavance MA, Rivest S. The HPA - immune axis and the immunomodulatory actions of glucocorticoids in the brain. Front Immunol. 2014;5:136. doi:10.3389/fimmu.2014.00136.

  3. Liu H, Boyatzis RE. Focusing on resilience and renewal from stress: the role of emotional and social intelligence competencies. Front Psychol. 2021;12:685829. doi:10.3389/fpsyg.2021.685829.

By Amber J. Tresca
Amber J. Tresca is a freelance writer and speaker who covers digestive conditions, including IBD. She was diagnosed with ulcerative colitis at age 16.