The hypothalamic-pituitary-adrenal (HPA) axis is a vital body system. The parts of the HPA axis include thehypothalamus, 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.
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Structure/Makeup
The HPA axis is made up of thehypothalamus, 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 hypothalamusis 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, includingcortisol, aldosterone, adrenaline, and noradrenaline.
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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 releasescorticotropin-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 hormonealso affects the pituitary gland. It tells the pituitary gland to start releasing adrenocorticotropic hormone.
Theadrenocorticotropic 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.
Function
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 orrun 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 thehypothalamus and the pituitary gland. It connects with receptors on the hypothalamus. This causes the HPA axis to slow down and stop the production ofcorticotropin-releasing and adrenocorticotropichormones.
Significance
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 theHPA 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
Summary
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.
National Institutes of Health.About adrenal gland disorders.
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.
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.
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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.
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FAQs
What is hypothalamic-pituitary adrenal HPA axis? ›
A major component of the homeostatic response is the hypothalamic-pituitary-adrenal (HPA) axis, an intricate, yet robust, neuroendocrine mechanism that mediates the effects of stressors by regulating numerous physiological processes, such as metabolism, immune responses, and the autonomic nervous system (ANS).
What is the HPA axis responsible for? ›The HPA axis is responsible for the neuroendocrine adaptation component of the stress response. This response is characterized by hypothalamic release of corticotropin-releasing factor (CRF). CRF is also known as CRH or corticotropin-releasing hormone.
What is part of the HPA axis? ›The hypothalamic-pituitary-adrenal axis, or HPA axis as it is commonly called, describes the interaction between the hypothalamus, pituitary gland, and adrenal glands. The hypothalamus and pituitary gland are located just above the brainstem, while the adrenal glands are found on top of the kidneys.
What part of the hypothalamus has the most direct role in the HPA axis? ›The hippocampus plays an important role in the terminating HPA axis responses to stress. Stimulation of hippocampal neurons decreases neuronal activity in the parvocellular division of the PVN and inhibits glucocorticoid secretion.
What is the HPA axis stress response? ›The hypothalamic-pituitary-adrenal axis, or HPA axis, is a term used to represent the interaction between the hypothalamus, pituitary gland, and adrenal glands; it plays an important role the body's response to stress. The pathway of the axis results in the production of cortisol.
How do you regulate the HPA axis? ›- Avoid Eating Processed, Refined Foods that Stress the HPA Axis. ...
- Avoid Dieting. ...
- Don't Skimp on Carbohydrates, but Be Sure to Choose Nutrient-Dense Carbs. ...
- Regulate Your Blood Sugar. ...
- Support Your Gut Microbiome.
Activation of the HPA axis causes secretion of glucocorticoids, which act on multiple organ systems to redirect energy resources to meet real or anticipated demand.
What are the three components of the HPA axis? ›The HPA axis is an important part of the neuroendocrine system and is involved in our bodily response to stress. The HPA axis has three primary components - the hypothalamus, the anterior and posterior pituitary glands, and the adrenal cortex.
What happens when HPA axis is suppressed? ›Suppression of the stress or HPA axis results in inadequate cortisol production. Cortisol is the natural stress hormone found in humans. When this hormone is produced insufficiently, response to stressors (e.g. trauma, surgery, inflammation) may be impaired and defence against infections may be inadequate.
Can stress affect your pituitary gland? ›During times of stress, the hypothalamus, a collection of nuclei that connects the brain and the endocrine system, signals the pituitary gland to produce a hormone, which in turn signals the adrenal glands, located above the kidneys, to increase the production of cortisol.
How does pain activate the HPA axis? ›
HPA axis activation by corticotropin-releasing hormone and vasopressin leads to an increase in circulating adrenocorticotropic hormone (ACTH) that results in cortisol production (or, in rodents, corticosterone production).
Can HPA axis be corrected? ›Cortisol output of the HPA axis can in reality be manipulated either directly or indirectly through several interventions. The most direct approaches involve (1) inhibition of cortisol synthesis at the level of the adrenal gland or (2) inhibition of CRH induced ACTH synthesis by the pituitary.
How do you test for HPA axis dysfunction? ›High-dose ACTH stimulation test: This test is used to evaluate the integrity of the HPA axis. It consists of the administration of 250 μg of intravenous corticotropin and measurement of serum cortisol concentrations after 30–60 min.
How long does it take to recover from HPA axis dysfunction? ›All patients demonstrated recovery of HPA axis by 10 weeks. Based on the above studies, it appears that most patients demonstrated recovery of HPA axis between 4–10 weeks after cessation of therapy.
How does the HPA axis regulate itself by using negative feedback? ›Negative Feedback
Once the stress response has been initiated, and cortisol enters the circulation, cortisol itself is able to act on the hypothalamus and pituitary and inhibit production of CRH and ACTH. This is called a negative feedback loop; the active hormone (cortisol) can shut off its own production.
Stress hormones include, but are not limited to: Cortisol, the main human stress hormone. Catecholamines such as adrenaline and norepinephrine. Vasopressin.
What happens when cortisol is released during stress? ›Cortisol, the primary stress hormone, increases sugars (glucose) in the bloodstream, enhances your brain's use of glucose and increases the availability of substances that repair tissues. Cortisol also curbs functions that would be nonessential or harmful in a fight-or-flight situation.
What does the pituitary gland release during stress? ›Hypothalamic-Pituitary-Adrenal (HPA) Axis
When we are experiencing something stressful, the hypothalamus releases a hormone called corticotropin-releasing hormone (CRH). CRH signals the pituitary gland to secrete a hormone called andrenocorticotropic hormone (ACTH) into the bloodstream.
- protein sources, like lean meats, fish, eggs, dairy, nuts, and legumes.
- leafy greens and colorful vegetables.
- whole grains.
- relatively low-sugar fruits.
- sea salt in moderation.
- healthy fats like olive oil and avocado.
As evidenced throughout, HPA axis hyperactivity can have many negative effects on sleep. It can lead to sleep fragmentation, decreased SWS, and shortened sleep time. Likewise, sleep disturbances can exacerbate HPA axis dysfunction, worsening the cycle.
How can I calm my pituitary gland? ›
One pre-meditation practice which is particularly recommended for pituitary health is Brahmari (Humming Bee) Breathing. In its simplest form we sit comfortably, relax and close the eyes and hum like a bee on the long outward breath. As we hum we will notice vibration in the bones of our head.
What happens if the hypothalamus stops working? ›Growth Hormone Deficiency: occurs when the hypothalamus is unable to stimulate the production and release of sufficient amounts of growth hormone necessary for development. This can result in slow growth, osteoporosis, muscle weakness, and high cholesterol levels.
How does the hypothalamus detect stress? ›After the amygdala sends a distress signal, the hypothalamus activates the sympathetic nervous system by sending signals through the autonomic nerves to the adrenal glands. These glands respond by pumping the hormone epinephrine (also known as adrenaline) into the bloodstream.
What does HPA stand for in medical terms? ›The Hypothalamic–Pituitary–adrenal (HPA) axis describes a complex set of positive and negative feedback influences between the hypothalamus, pituitary gland, and adrenal gland.
What are all the functions of the hypothalamus? ›The hypothalamus helps manage your body temperature, hunger and thirst, mood, sex drive, blood pressure and sleep.
Where is cortisol produced from? ›Cortisol is a steroid hormone that is produced by the adrenal glands, which sit on top of each kidney. When released into the bloodstream, cortisol can act on many different parts of the body and can help: the body respond to stress or danger. increase the body's metabolism of glucose.
How do you treat adrenal insufficiency? ›Primary adrenal insufficiency — Treatment of adrenal insufficiency requires a daily dose of a glucocorticoid and mineralocorticoid pills, usually for life. Androgen replacement may be recommended for women. The goal of treatment is to stabilize hormone levels and relieve symptoms.
How does adrenal insufficiency affect the body? ›The most common symptoms are fatigue, muscle weakness, loss of appetite, weight loss, and abdominal pain. Adrenal insufficiency can be caused by autoimmune disease or suddenly stopping steroid medicines used to treat other conditions, among other causes.
What is the anger hormone called? ›Recognizing anger
Anger causes a physical reaction in the body. It releases adrenaline, the “fight-or-flight” hormone that prepares a person for conflict or danger. This can have the following effects: a rapid heartbeat.
A sudden loss of blood can damage your pituitary gland (known as necrosis). This can happen with Sheehan syndrome (severe blood loss after childbirth), sickle cell anemia and diabetes. A subarachnoid hemorrhage (SAH), a kind of stroke usually from a head injury, can also cause pituitary apoplexy.
What are 5 emotional signs of stress? ›
- Crying spells or bursts of anger.
- Difficulty eating.
- Losing interest in daily activities.
- Increasing physical distress symptoms such as headaches or stomach pains.
- Fatigue.
- Feeling guilty, helpless, or hopeless.
- Avoiding family and friends.
Stress can make chronic pain worse. Stress causes your muscles to tense or spasm, which increases pain. When you feel stressed, levels of the hormone cortisol rise. This can cause inflammation and pain over time.
What part of the nervous system does the hypothalamus interact with? ›The hypothalamus is involved in many functions of the autonomic nervous system, as it receives information from nearly all parts of the nervous system. As such, it is considered the link between the nervous system and the endocrine system.
How does increased cortisol make you more afraid? ›Cortisol increases the return of fear by strengthening amygdala signaling in men. Psychoneuroendocrinology.
What is the best supplement to reduce cortisol? ›- Ashwagandha. ...
- Omega-3 Fatty Acids. ...
- Prebiotics and Probiotics. ...
- Cordyceps Sinensis. ...
- Phosphatidylserine. ...
- L-Theanine.
- Eat a balanced diet. While eating a balanced diet is important for every body part, it's especially crucial when it comes to the hypothalamus. ...
- Get enough sleep. A 2014 study in rats found that sleep deprivation was associated with hypothalamic dysfunction. ...
- Exercise regularly.
Antidepressants are an effective treatment for depressive and anxiety disorders. Those disorders are frequently accompanied by heightened cortisol levels. Antidepressants may affect hypothalamic–pituitary–adrenal axis functioning, the alteration of which could be partially responsible for treatment efficacy.
What happens when the HPA axis is activated? ›Activation of the HPA axis causes secretion of glucocorticoids, which act on multiple organ systems to redirect energy resources to meet real or anticipated demand.
How is the hypothalamic pituitary adrenal HPA axis shut off? ›2-Minute Neuroscience: HPA Axis - YouTube
What changes occur in the hypothalamic adrenal axis with stress? ›With repeated exposure to stress, the sensitized HPA axis may continue to hypersecrete CRH from the hypothalamus. Over time, CRH receptors in the anterior pituitary will become down-regulated, producing depression and anxiety symptoms.
Why is cortisol released during stress? ›
Regulating your body's stress response: During times of stress, your body can release cortisol after releasing its “fight or flight” hormones, such as adrenaline, so you continue to stay on high alert. In addition, cortisol triggers the release of glucose (sugar) from your liver for fast energy during times of stress.
Can HPA axis be corrected? ›Cortisol output of the HPA axis can in reality be manipulated either directly or indirectly through several interventions. The most direct approaches involve (1) inhibition of cortisol synthesis at the level of the adrenal gland or (2) inhibition of CRH induced ACTH synthesis by the pituitary.
What happens when HPA axis is suppressed? ›Suppression of the stress or HPA axis results in inadequate cortisol production. Cortisol is the natural stress hormone found in humans. When this hormone is produced insufficiently, response to stressors (e.g. trauma, surgery, inflammation) may be impaired and defence against infections may be inadequate.
Can stress affect your pituitary gland? ›During times of stress, the hypothalamus, a collection of nuclei that connects the brain and the endocrine system, signals the pituitary gland to produce a hormone, which in turn signals the adrenal glands, located above the kidneys, to increase the production of cortisol.
How does pain activate the HPA axis? ›HPA axis activation by corticotropin-releasing hormone and vasopressin leads to an increase in circulating adrenocorticotropic hormone (ACTH) that results in cortisol production (or, in rodents, corticosterone production).
What are the 3 stress hormones? ›Stress hormones include, but are not limited to: Cortisol, the main human stress hormone. Catecholamines such as adrenaline and norepinephrine. Vasopressin.
What does the pituitary gland release during stress? ›Hypothalamic-Pituitary-Adrenal (HPA) Axis
When we are experiencing something stressful, the hypothalamus releases a hormone called corticotropin-releasing hormone (CRH). CRH signals the pituitary gland to secrete a hormone called andrenocorticotropic hormone (ACTH) into the bloodstream.
Together, these data indicate that robust activation of the HPA axis increases inflammation through action on multiple tissues. While GCs have potent anti-inflammatory effects, excessive GC release in response to HPA axis activation can contribute to increased inflammation.
How does chronic stress affect HPA axis? ›Chronic and repeated stressors can lead to one or more forms of HPA axis dysregulation, altering appropriate cortisol secretion and affecting end-organ function (see sections on Hypercortisolism and Hypocortisolism for mechanisms and therapeutic considerations).
What happens if the hypothalamus stops working? ›Growth Hormone Deficiency: occurs when the hypothalamus is unable to stimulate the production and release of sufficient amounts of growth hormone necessary for development. This can result in slow growth, osteoporosis, muscle weakness, and high cholesterol levels.
What part of the brain calms you down? ›
The prefrontal cortex is a big region in the front of the brain (Figure 1). It can be called the control center of our brains because it helps to control our thoughts and actions. The main job of the prefrontal cortex is to control our emotional responses to stress so that we do not get too stressed out.
What blood tests increase stress? ›A cortisol blood test is one of the most commonly used blood tests. Cortisol is a hormone that is released by the adrenal glands when one is under stress. Higher levels of cortisol would indicate higher levels of stress.
What does too much cortisol feel like? ›According to Mayo Clinic, signs and symptoms associated with excess cortisol levels can include: Rapid weight gain mainly in the face, chest, and abdomen. A flushed and round face. High blood pressure.