Hypothalamic-pituitary-adrenal axis

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Hypothalamic-pituitary-adrenal axis

The hypothalamic-pituitary-adrenal axis (HPA or HTPA axis), also known as the limbic-hypothalamic-pituitary-adrenal axis (LHPA axis), is a complex set of direct influences and feedback

Feedback

Feedback describes the situation when output from an event or phenomenon in the past will influence the same event/phenomenon in the present or future....
interactions among the hypothalamus

Hypothalamus

Pituitary gland

The pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g . It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a Dura mater fold ....
(a pea-shaped structure located below the hypothalamus), and the adrenal (or suprarenal

Suprarenal

Suprarenal is an adjective that can refer to:* Adrenal gland* Suprarenal veins...
) glands (small, conical organs on top of the kidneys).

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Encyclopedia

The hypothalamic-pituitary-adrenal axis (HPA or HTPA axis), also known as the limbic-hypothalamic-pituitary-adrenal axis (LHPA axis), is a complex set of direct influences and feedback

Feedback

Feedback describes the situation when output from an event or phenomenon in the past will influence the same event/phenomenon in the present or future....
interactions among the hypothalamus

Hypothalamus

Pituitary gland

Suprarenal

Suprarenal is an adjective that can refer to:* Adrenal gland* Suprarenal veins...
) glands (small, conical organs on top of the kidneys). The interactions among these organs constitute the HPA axis, a major part of the neuroendocrine system

Neuroendocrinology

Neuroendocrinology is the study of the interactions between the nervous system and the endocrine system. The concept arose from the recognition that the secretion of hormones from the pituitary gland is closely controlled by the brain, especially by the hypothalamus....
that controls reactions to stress

Stress (medicine)

Stress is a biological term which refers to the consequences of the failure of a human or animal body to respond appropriately to emotional or body threats to the organism, whether actual or imagined....
and regulates many body processes, including digestion

Digestion

Digestion is the mechanical and chemical breaking down of food into smaller components, to a form that can be Absorption, for instance, by a blood stream....
, the immune system

Immune system

An immune system is a collection of biological processes within an organism that protects against disease by identifying and killing pathogens and tumour cells....
, mood and emotions, sexuality, and energy storage and expenditure. A wide variety of species, from the most ancient organisms to humans, share components of the HPA axis. It is the common mechanism for interactions among glands, hormones, and parts of the midbrain that mediate the general adaptation syndrome (GAS).

Anatomy

The key elements of the HPA axis are:

The paraventricular nucleus
Paraventricular nucleus

The paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes....
of the hypothalamus
Hypothalamus

The hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
, which contains neuroendocrine
Neuroendocrine

Neuroendocrine [IPA n??ro?'?nd?kr?n] cells are cells that release a hormone into the circulating blood in response to a neural stimulus. These hormones may be amines, neuropeptides, or specialized amino acids....
neurons that synthesize and secrete vasopressin
Vasopressin

Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a hormone found in most mammals, including humans....
and corticotropin-releasing hormone
Corticotropin-releasing hormone

Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress ....
(CRH). These two peptides regulate:

The anterior lobe of the pituitary gland
Pituitary gland

The pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g . It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a Dura mater fold ....
. In particular, CRH and vasopressin stimulate the secretion of adrenocorticotropic hormone
Adrenocorticotropic hormone

Adrenocorticotropic hormone is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress ....
(ACTH), once known as corticotropin. ACTH in turn acts on:
the adrenal cortices
Adrenal cortex

Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively....
, which produce glucocorticoid
Glucocorticoid

Glucocorticoids are a class of steroid hormones which bind to the glucocorticoid receptor , which is present in almost every animal cell.GCs are part of the feedback mechanism in the immune system which turns immune activity down....
hormones (mainly cortisol
Cortisol

Cortisol is a corticosteroid hormone or glucocorticoid produced by the adrenal cortex, that is part of the adrenal gland . It is usually referred to as the "stress hormone" as it is involved in response to stress and anxiety, controlled by Corticotropin-releasing hormone....
in humans) in response to stimulation by ACTH. Glucocorticoids in turn act back on the hypothalamus and pituitary (to suppress CRH and ACTH production) in a negative feedback cycle.

CRH and vasopressin are released from neurosecretory nerve terminals at the median eminence

Median eminence

The median eminence is part of the inferior boundary for the hypothalamus part of the human brain. A small swelling on the tuber cinereum posterior to the infundibulum - atop the pituitary stalk - the median eminence lies in the area roughly bounded on its posterolateral region by the cerebral peduncles, and on its anterolateral region...
. They are transported to the anterior pituitary through the portal blood vessel system of the hypophyseal stalk. There, CRH and vasopressin act synergistically to stimulate the secretion of stored ACTH from corticotrope cells. ACTH is transported by the blood

Blood

Blood is a specialized bodily fluid that delivers necessary substances to the body's Cell s ? such as nutrients and oxygen ? and transports waste products away from those same cells....
to the adrenal cortex

Adrenal cortex

Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively....
of the adrenal gland

Adrenal gland

In mammals, the adrenal glands are the star-shaped endocrine glands that sit on top of the kidneys; their name indicates that position . They are chiefly responsible for regulating the stress response through the biosynthesis of corticosteroids and catecholamines, including cortisol and adrenaline, respectively....
, where it rapidly stimulates biosynthesis of corticosteroid

Corticosteroid

Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiology systems such as stress , immune system and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior....
s such as cortisol from cholesterol

Cholesterol

Cholesterol is a lipidic, waxy alcohol found in the cell membranes and transported in the blood plasma of all animals. It is an essential component of mammalian cell membranes where it is required to establish proper membrane permeability and membrane fluidity....
. Cortisol is a major stress hormone and has effects on many tissues in the body, including on the brain. In the brain, cortisol acts at two types of receptor - mineralocorticoid receptors and glucocorticoid receptors, and these are expressed by many different types of neurons. One important target of glucocorticoids is the hypothalamus

Hypothalamus

The hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
, which is a major controlling centre of the HPA axis.

Vasopressin can be thought of as "water conservation hormone" and is also known as "antidiuretic hormone." It is released when the body is dehydrated and has potent water-conserving effects on the kidney. It is also a potent vasoconstrictor.

Important to the function of the HPA axis are some of the feedback loops:

Cortisol produced in the adrenal cortex will negatively feedback to inhibit both the hypothalamus and the pituitary gland. This reduces the secretion of CRH and vasopressin, and also directly reduces the cleavage of proopiomelanocortin
Proopiomelanocortin

Pro-opiomelanocortin is a precursor polypeptide with 241 amino acid residues.This gene encodes a polypeptide hormone precursor that undergoes extensive, tissue-specific, post-translational processing via cleavage by subtilisin-like enzymes known as Proprotein convertase....
(POMC) into ACTH and ß-endorphins.
Epinephrine
Epinephrine

Epinephrine is a hormone and neurotransmitter.Epinephrine increases the "fight or flight" response of the Sympathetic nervous system of the autonomic nervous system....
and norepinephrine
Norepinephrine

Norepinephrine or noradrenaline is a catecholamine with dual roles as a hormone and a neurotransmitter.As a stress hormone, norepinephrine affects parts of the brain where attention and responding actions are controlled....
are produced by the adrenal medulla through sympathetic stimulation and the local effects of cortisol (upregulation enzymes to make E/NE). E/NE will positively feedback to the pituitary and increase the breakdown of POMCs into ACTH and ß-endorphins.

Function

Release of CRH from the hypothalamus is influenced by stress

Stress (medicine)

Stress is a biological term which refers to the consequences of the failure of a human or animal body to respond appropriately to emotional or body threats to the organism, whether actual or imagined....
, by blood levels of cortisol and by the sleep/wake cycle

Sleep

Sleep is the natural state of bodily rest observed in humans and other animals. It is common to all mammals and birds, and is also seen in many reptiles, amphibians and fish....
. In healthy individuals, cortisol rises rapidly after wakening, reaching a peak within 30-45 minutes. It then gradually falls over the day, rising again in late afternoon. Cortisol levels then fall in late evening, reaching a trough during the middle of the night. An abnormally flattened circadian cortisol cycle has been linked with chronic fatigue syndrome

Chronic fatigue syndrome

Chronic fatigue syndrome is the most common name given to a poorly understood, variably debilitating disorder or disorders of uncertain etiology....
(MacHale, 1998), insomnia

Insomnia

Insomnia is a symptom of a sleep disorder characterized by persistent difficulty falling sleep or staying asleep despite the opportunity. Insomnia is a symptom, not a stand-alone diagnosis or a disease....
(Backhaus, 2004) and burnout

Burnout (psychology)

Burnout is a psychology term for the experience of long-term exhaustion and diminished interest. Musicians, authors, teachers, athletes, engineers, emergency service, vocational rehabilitation counselors, soldiers, reporters and High tech seem more prone to burnout than others....
(Pruessner, 1999).

Anatomical connections between brain areas such as the amygdala

Amygdala

Hippocampus

The hippocampus is a brain structure located inside the medial temporal lobe of the cerebral cortex, and therefore is part of the telencephalon ....
, and hypothalamus facilitate activation of the HPA axis. Sensory information arriving at the lateral aspect of the amygdala

Amygdala

The are almond-shaped groups of neurons located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotions, the amygdalae are considered part of the limbic system....
is processed and conveyed to the central nucleus, which projects to several parts of the brain involved in responses to fear. At the hypothalamus, fear-signaling impulses activate both the sympathetic nervous system

Sympathetic nervous system

The Sympathetic Nervous System is a branch of the autonomic nervous system along with the enteric nervous system and parasympathetic nervous system....
and the modulating systems of the HPA axis.

Increased production of cortisol mediates alarm reactions to stress, facilitating an adaptive phase of a general adaptation syndrome in which alarm reactions including the immune response are suppressed, allowing the body to attempt countermeasures.

Glucocorticoids have many important functions, including modulation of stress reactions, but in excess they can be damaging. Atrophy

Atrophy

Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include poor nourishment, poor circulatory system, loss of hormone support, loss of nerve supply to the target Organ , disuse or lack of exercise or disease intrinsic to the tissue itself....
of the hippocampus in humans and animals exposed to severe stress is believed to be caused by prolonged exposure to high concentrations of glucocorticoid

Glucocorticoid

Glucocorticoids are a class of steroid hormones which bind to the glucocorticoid receptor , which is present in almost every animal cell.GCs are part of the feedback mechanism in the immune system which turns immune activity down....
s. Deficiencies of the hippocampus

Hippocampus

The hippocampus is a brain structure located inside the medial temporal lobe of the cerebral cortex, and therefore is part of the telencephalon ....
may reduce the memory resources available to help a body formulate appropriate reactions to stress.

The HPA axis is involved in the neurobiology of mood disorder

Mood disorder

A mood disorder is the term given for a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's Mood is hypothesised to be the main underlying feature....
s and functional illnesses, including anxiety disorder

Anxiety disorder

Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fears and anxieties.Although in casual discourse the words anxiety, fear, and phobia are often used interchangeably, in clinical usage, they have distinct meanings....
, bipolar disorder

Bipolar disorder

Bipolar disorder is a Classification of mental disorders that describes a category of mood disorders, or mood swings, defined by the presence of one or more episodes of abnormally elevated mood clinically referred to as mania or, if milder, hypomania....
, insomnia

Insomnia

Post-traumatic stress disorder

Posttraumatic stress disorder is an anxiety disorder that can develop after exposure to one or more traumatic events that threatened or caused grave physical harm....
, ADHD, major depressive disorder, burnout

Burnout (psychology)

Chronic fatigue syndrome

Chronic fatigue syndrome is the most common name given to a poorly understood, variably debilitating disorder or disorders of uncertain etiology....
, fibromyalgia

Fibromyalgia

Fibromyalgia , meaning muscle and connective tissue pain , is a disorder classified by the presence of chronic widespread pain and a heightened and painful response to gentle Somatosensory system ....
, irritable bowel syndrome

Irritable bowel syndrome

Irritable bowel syndrome , also called spastic colon, is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any organic cause....
, and alcoholism

Alcoholism

Alcoholism is a term with multiple and sometimes conflicting definitions to describe the detrimental effects of alcohol intake.In common and historic usage, alcoholism refers to any condition that results in the continued consumption of alcoholic beverages despite health problems and negative social consequences....
. Antidepressants, which are routinely prescribed for many of these illnesses, serve to regulate HPA axis function.

Research

Experimental studies have investigated many different types of stress, and their effects on the HPA axis in many different circumstances. Stressors can be of many different types - in experimental studies in rats, a distinction is often made between "social stress" and "physical stress", but both types activate the HPA axis, though via different pathways.Several monoamine neurotransmitters are important in regulating the HPA axis, especially dopamine

Dopamine

Dopamine is a neurotransmitter occurring in a wide variety of animals, including both vertebrates and invertebrates. In the human brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors ? D1, D2, D3, D4 and D5, and their variants....
, serotonin

Serotonin

Serotonin is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system and enterochromaffin cells in the gastrointestinal tract of animals including humans....
and norepinephrine

Norepinephrine

Norepinephrine or noradrenaline is a catecholamine with dual roles as a hormone and a neurotransmitter.As a stress hormone, norepinephrine affects parts of the brain where attention and responding actions are controlled....
(noradrenaline). In herbal medicine, adaptogen

Adaptogen

The term adaptogen is used by herbalists to refer to a natural herb product that is proposed to increase the body's resistance to stress, Physical trauma, anxiety and Fatigue ....
s work by reregulating the HPA axis.

The HPA axis is a feature of other vertebrates as well as of mammals. For example, biologists studying stress in fish showed that social subordination leads to chronic stress, related to reduced aggressive

Aggression

In psychology, as well as other social science and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause pain or harm....
interactions, to lack of control

Impulsivity

Impulsivity is a type of human behavior characterized by the inclination of an individual to act on impulse rather than thought. Although part of the normal behavior, impulsivity also plays a role in many mental illnesses....
and to the constant threat imposed by dominant fish. Serotonin (5HT) appeared to be the active neurotransmitter involved in mediating stress responses, and increases in serotonin are related to increased plasma

Blood

Salmon

Salmon is the common name for several species of fish of the family Salmonidae. Several other fish in the family are called trout,the difference is often attributed to the migratory life of the salmon as compared to the residential behaviour of trout, this holds true for the Atlantic salmon....
oid fish), activation of the HPA axis, and inhibition of aggression. Inclusion of the amino acid

Amino acid

In chemistry, an amino acid is a molecule containing both amine and carboxyl functional groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent....
L-tryptophan, a precursor of 5HT, in the feed of rainbow trout

Trout

Trout are a number of species of freshwater fish belonging to the Salmoninae subfamily of the Salmonidae family. Salmon belong to some of the same genera as trout but, unlike most trout, most salmon species spend almost all their lives in salt water....
made the trout less aggressive and less responsive to stress However, the study mentions that plasma cortisol was not affected by dietary L-tryptophan.

Hypothalamic-pituitary-adrenal axis

Anatomy

Function

Research

See also

General

Relation to illnesses

External links