The adrenal glands (also known as suprarenal glands) are
endocrine gland
Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid ...
s that produce a variety of hormones including
adrenaline
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
and the steroids
aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
and
cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
.
They are found above the
kidneys
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
. Each gland has an outer
cortex
Cortex or cortical may refer to:
Biology
* Cortex (anatomy), the outermost layer of an organ
** Cerebral cortex, the outer layer of the vertebrate cerebrum, part of which is the ''forebrain''
*** Motor cortex, the regions of the cerebral cortex i ...
which produces
steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Wi ...
s and an inner
medulla
Medulla or Medullary may refer to:
Science
* Medulla oblongata, a part of the brain stem
* Renal medulla, a part of the kidney
* Adrenal medulla, a part of the adrenal gland
* Medulla of ovary, a stroma in the center of the ovary
* Medulla of th ...
. The
adrenal cortex
The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is ...
itself is divided into three main zones: the
zona glomerulosa
The ''zona glomerulosa'' (sometimes, glomerular zone) of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the renal capsule. Its cells are ovoid and arranged in clusters or arches (''glomus'' is Latin ...
, the
zona fasciculata
The ''zona fasciculata'' (sometimes, fascicular or fasciculate zone) constitutes the middle and also the widest zone of the adrenal cortex, sitting directly beneath the ''zona glomerulosa''. Constituent cells are organized into bundles or "fascicl ...
and the
zona reticularis
The zona reticularis (sometimes, reticulate zone) is the innermost layer of the adrenal cortex, lying deep to the zona fasciculata and superficial to the adrenal medulla. The cells are arranged cords that project in different directions giving a n ...
.
The adrenal cortex produces three main types of
steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Wi ...
s:
mineralocorticoid
Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary mi ...
s,
glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s, and
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
s. Mineralocorticoids (such as
aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
) produced in the zona glomerulosa help in the regulation of blood pressure and
electrolyte balance
An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon dis ...
. The glucocorticoids
cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
and
cortisone
Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug; it is not synthesized in the adrenal glands. Cortisol is converted by the action of the enzy ...
are synthesized in the zona fasciculata; their functions include the regulation of
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
and
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
suppression. The innermost layer of the cortex, the zona reticularis, produces androgens that are converted to fully functional sex hormones in the
gonad
A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...
s and other target organs.
The production of steroid hormones is called
steroidogenesis
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
, and involves a number of reactions and processes that take place in cortical cells.
The medulla produces the
catecholamine
A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine.
Catechol can be either a free molecule or a subst ...
s, which function to produce a
rapid response throughout the body in
stress
Stress may refer to:
Science and medicine
* Stress (biology), an organism's response to a stressor such as an environmental condition
* Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
situations.
A number of
endocrine disease
Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.
Types of disease
Broadly speaking, endocrine disorders may be subdivided into three groups:
# Endocrin ...
s involve dysfunctions of the adrenal gland. Overproduction of cortisol leads to
Cushing's syndrome
Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, ...
, whereas insufficient production is associated with
Addison's disease
Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal ...
.
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex. ...
is a genetic disease produced by dysregulation of endocrine control mechanisms.
A variety of
tumors
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
can arise from adrenal tissue and are commonly found in
medical imaging
Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...
when searching for other diseases.
Structure
![Adrenal glands](https://upload.wikimedia.org/wikipedia/commons/1/15/Adrenal_glands.jpg)
The adrenal glands are located on both sides of the body in the
retroperitoneum
The retroperitoneal space (retroperitoneum) is the anatomical space (sometimes a potential space) behind (''retro'') the peritoneum. It has no specific delineating anatomical structures. Organs are retroperitoneal if they have peritoneum on their ...
, above and slightly
medial to the
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s. In humans, the right adrenal gland is pyramidal in shape, whereas the left is semilunar or crescent shaped and somewhat larger.
The adrenal glands measure approximately 5 cm in length, 3 cm in width, and up to 1 cm in thickness. Their combined weight in an adult human ranges from 7 to 10 grams. The glands are yellowish in colour.
The adrenal glands are surrounded by a
fatty capsule and lie within the
renal fascia
The renal fascia is a layer of connective tissue encapsulating the kidneys and the adrenal glands. It can be divided into:
*The anterior renal fascia, also called Gerota's fascia (after Dimitrie Gerota)
*The posterior renal fascia, also called Zuc ...
, which also surrounds the kidneys. A weak
septum
In biology, a septum (Latin for ''something that encloses''; plural septa) is a wall, dividing a cavity or structure into smaller ones. A cavity or structure divided in this way may be referred to as septate.
Examples
Human anatomy
* Interatri ...
(wall) of
connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
separates the glands from the kidneys.
The adrenal glands are directly below the
diaphragm
Diaphragm may refer to:
Anatomy
* Thoracic diaphragm, a thin sheet of muscle between the thorax and the abdomen
* Pelvic diaphragm or pelvic floor, a pelvic structure
* Urogenital diaphragm or triangular ligament, a pelvic structure
Other
* Diap ...
, and are attached to the
crura of the diaphragm
The crus of diaphragm (pl. crura), refers to one of two tendon, tendinous structures that extends below the thoracic diaphragm, diaphragm to the vertebral column. There is a right crus and a left crus, which together form a tether for muscular cont ...
by the renal fascia.
Each adrenal gland has two distinct parts, each with a unique function, the outer
adrenal cortex
The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is ...
and the inner
medulla
Medulla or Medullary may refer to:
Science
* Medulla oblongata, a part of the brain stem
* Renal medulla, a part of the kidney
* Adrenal medulla, a part of the adrenal gland
* Medulla of ovary, a stroma in the center of the ovary
* Medulla of th ...
, both of which produce hormones.
Adrenal cortex
![Adrenal cortex labelled](https://upload.wikimedia.org/wikipedia/commons/c/c6/Adrenal_cortex_labelled.jpg)
The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones.
The adrenal cortex is the outermost layer of the adrenal gland. Within the cortex are three layers, called "zones". When
viewed under a microscope each layer has a distinct appearance, and each has a different function.
The
adrenal cortex
The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is ...
is devoted to production of
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s, namely
aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
,
cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
, and
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
s.
Zona glomerulosa
The outermost zone of the adrenal cortex is the
zona glomerulosa
The ''zona glomerulosa'' (sometimes, glomerular zone) of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the renal capsule. Its cells are ovoid and arranged in clusters or arches (''glomus'' is Latin ...
. It lies immediately under the fibrous capsule of the gland. Cells in this layer form oval groups, separated by
thin strands of connective tissue from the fibrous capsule of the gland and carry wide
capillaries
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
.
This layer is the main site for production of
aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
, a
mineralocorticoid
Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary mi ...
, by the action of the enzyme
aldosterone synthase
Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzyme ...
.
Aldosterone plays an important role in the long-term
regulation of blood pressure.
Zona fasciculata
The
zona fasciculata
The ''zona fasciculata'' (sometimes, fascicular or fasciculate zone) constitutes the middle and also the widest zone of the adrenal cortex, sitting directly beneath the ''zona glomerulosa''. Constituent cells are organized into bundles or "fascicl ...
is situated between the zona glomerulosa and zona reticularis. Cells in this layer are responsible for producing
glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s such as
cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
.
It is the largest of the three layers, accounting for nearly 80% of the volume of the cortex.
In the zona fasciculata, cells are arranged in columns radially oriented towards the medulla. Cells contain numerous lipid droplets, abundant
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
and a complex
smooth endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
.
Zona reticularis
The innermost cortical layer, the
zona reticularis
The zona reticularis (sometimes, reticulate zone) is the innermost layer of the adrenal cortex, lying deep to the zona fasciculata and superficial to the adrenal medulla. The cells are arranged cords that project in different directions giving a n ...
, lies directly adjacent to the medulla. It produces
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
s, mainly
dehydroepiandrosterone
Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It functio ...
(DHEA),
DHEA sulfate
Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroepiand ...
(DHEA-S), and
androstenedione
Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepia ...
(the precursor to
testosterone
Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
) in humans.
Its small cells form irregular cords and clusters, separated by capillaries and connective tissue. The cells contain relatively small quantities of cytoplasm and lipid droplets, and sometimes display brown
lipofuscin
Lipofuscin is the name given to fine yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion. It is considered to be one of the aging or "wear-and-tear" pigments, found in the liver, kidney, heart muscle, retin ...
pigment.
Medulla
The
adrenal medulla
The adrenal medulla ( la, medulla glandulae suprarenalis) is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cel ...
is at the centre of each adrenal gland, and is surrounded by the adrenal cortex. The
chromaffin cell
Chromaffin cells, also called pheochromocytes (or phaeochromocytes), are neuroendocrine cells found mostly in the medulla of the adrenal glands in mammals. These cells serve a variety of functions such as serving as a response to stress, monitor ...
s of the medulla are the body's main source of the
catecholamine
A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine.
Catechol can be either a free molecule or a subst ...
s, such as adrenaline and noradrenaline, released by the medulla. Approximately 20% noradrenaline (norepinephrine) and 80% adrenaline (epinephrine) are secreted here.
The adrenal medulla is driven by the
sympathetic nervous system
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...
via
preganglionic fiber
In the autonomic nervous system, fibers from the CNS to the ganglion are known as preganglionic fibers. All preganglionic fibers, whether they are in the sympathetic division or in the parasympathetic division, are cholinergic (that is, these f ...
s originating in the
thoracic spinal cord
A spinal nerve is a mixed nerve, which carries motor, sensory, and autonomic signals between the spinal cord and the body. In the human body there are 31 pairs of spinal nerves, one on each side of the vertebral column. These are grouped into the ...
, from vertebrae T5–T11.
Because it is innervated by
preganglionic nerve fibers
In the autonomic nervous system, fibers from the CNS to the ganglion are known as preganglionic fibers. All preganglionic fibers, whether they are in the sympathetic division or in the parasympathetic division, are cholinergic (that is, these ...
, the adrenal medulla can be considered as a specialized
sympathetic ganglion
The sympathetic ganglia, or paravertebral ganglia are autonomic ganglia, of the sympathetic nervous system. Ganglia are 20,000 to 30,000 afferent and efferent nerve cell bodies that run along on either side of the spinal cord. Afferent nerve cel ...
.
Unlike other sympathetic ganglia, however, the adrenal medulla lacks distinct synapses and releases its secretions directly into the blood.
Blood supply
The adrenal glands have one of the greatest blood supply rates per gram of tissue of any organ: up to 60
small arteries may enter each gland.
Three arteries usually supply each adrenal gland:
* The
superior suprarenal artery
The superior suprarenal artery is an artery in the abdomen. It is a branch of the inferior phrenic artery, itself a branch of the aorta. It supplies the adrenal gland.
Structure
The superior suprarenal artery is a branch of the inferior phreni ...
, a branch of the
inferior phrenic artery
The inferior phrenic arteries are two small vessels which supply the diaphragm. They present much variety in their origin.
Structure
Origin
The inferior phrenic arteries usually arise between T12 and L2 vertebrae. They may arise separately ...
* The
middle suprarenal artery
The middle suprarenal artery (middle capsular artery) is a paired artery in the abdomen. It is a branch of the aorta. It supplies the adrenal gland.
Structure
Origin
The middle suprarenal artery (usually) arises from lateral aspect of the ...
, a direct branch of the
abdominal aorta
In human anatomy, the abdominal aorta is the largest artery in the abdominal cavity. As part of the aorta, it is a direct continuation of the descending aorta (of the thorax).
Structure
The abdominal aorta begins at the level of the thoracic d ...
* The
inferior suprarenal artery
The inferior suprarenal artery is a paired artery that supplies the adrenal gland. It usually originates at the trunk of the renal artery before its terminal division, but with many common variations. It supplies the adrenal gland parenchyma, th ...
, a branch of the
renal artery
The renal arteries are paired arteries that supply the kidneys with blood. Each is directed across the crus of the diaphragm, so as to form nearly a right angle.
The renal arteries carry a large portion of total blood flow to the kidneys. Up to a ...
These blood vessels supply a network of small arteries within the capsule of the adrenal glands. Thin strands of the capsule enter the glands, carrying blood to them.
Venous blood
Venous blood is deoxygenated blood which travels from the peripheral blood vessels, through the venous system into the right atrium of the heart. Deoxygenated blood is then pumped by the right ventricle to the lungs via the pulmonary artery whic ...
is drained from the glands by the
suprarenal veins
The suprarenal veins are two in number:
* the ''right'' ends in the inferior vena cava.
* the ''left'' ends in the left renal or left inferior phrenic vein.
They receive blood from the adrenal glands and will sometimes form anastomoses with the in ...
, usually one for each gland:
* The
right suprarenal vein drains into the
inferior vena cava
The inferior vena cava is a large vein that carries the deoxygenated blood from the lower and middle body into the right atrium of the heart. It is formed by the joining of the right and the left common iliac veins, usually at the level of the ...
* The
left suprarenal vein
The suprarenal veins are two in number:
* the ''right'' ends in the inferior vena cava.
* the ''left'' ends in the left renal or left inferior phrenic vein.
They receive blood from the adrenal glands and will sometimes form anastomoses
An anast ...
drains into the left
renal vein
The renal veins are large-calibre veins that drain blood filtered by the kidneys into the inferior vena cava. There is one renal vein draining each kidney.
Because the inferior vena cava is on the right half of the body, the left renal vein is lo ...
or the left
inferior phrenic vein
The inferior phrenic veins drain the diaphragm and follow the course of the inferior phrenic arteries;
* the right ends in the inferior vena cava;
* the left is often represented by two branches,
** one of which ends in the left renal or suprar ...
.
The central adrenomedullary vein, in the adrenal medulla, is an unusual type of blood vessel. Its structure is different from the other veins in that the
smooth muscle
Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
in its
tunica media
The tunica media (New Latin "middle coat"), or media for short, is the middle tunica (layer) of an artery or vein. It lies between the tunica intima on the inside and the tunica externa on the outside.
Artery
Tunica media is made up of smooth m ...
(the middle layer of the vessel) is arranged in conspicuous, longitudinally oriented bundles.
Variability
The adrenal glands may not develop at all, or may be fused in the midline behind the
aorta
The aorta ( ) is the main and largest artery in the human body, originating from the left ventricle of the heart and extending down to the abdomen, where it splits into two smaller arteries (the common iliac arteries). The aorta distributes ...
.
These are associated with other
congenital abnormalities
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can r ...
, such as failure of the kidneys to develop, or fused kidneys.
The gland may develop with a partial or complete absence of the cortex, or may develop in an unusual location.
Function
![1818 The Adrenal Glands](https://upload.wikimedia.org/wikipedia/commons/c/ca/1818_The_Adrenal_Glands.jpg)
The adrenal gland secretes a number of different hormones which are metabolised by
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s either within the gland or in other parts of the body. These hormones are involved in a number of essential biological functions.
Corticosteroids
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s are a group of steroid hormones produced from the cortex of the adrenal gland, from which they are named.
* Mineralocorticoids such as
aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
regulate salt ("mineral") balance and blood pressure
[Marieb Human Anatomy & Physiology 9th edition, chapter:16, page:629, question number:14]
* Glucocorticoids such as
cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
influence metabolism rates of proteins, fats and sugars ("glucose").
*Androgens such as
dehydroepiandrosterone
Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It functio ...
.
;Mineralocorticoids
The adrenal gland produces
aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
, a
mineralocorticoid
Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary mi ...
, which is important in the regulation of salt ("mineral") balance and
blood volume
Blood volume (volemia) is the volume of blood (blood cells and plasma) in the circulatory system of any individual.
Humans
A typical adult has a blood volume of approximately 5 liters, with females and males having approximately the same blood per ...
. In the kidneys, aldosterone acts on the
distal convoluted tubule
The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule.
Physiology
It is partly responsible for the regulation of potassium, sodium, calcium, and pH.
On its apical surface (lumen ...
s and the
collecting ducts
The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in elect ...
by increasing the reabsorption of
sodium
Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
and the excretion of both potassium and hydrogen ions.
Aldosterone is responsible for the reabsorption of about 2% of filtered
glomerular filtrate. Sodium retention is also a response of the distal colon and sweat glands to aldosterone receptor stimulation.
Angiotensin II
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adre ...
and extracellular
potassium
Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
are the two main regulators of aldosterone production.
The amount of sodium present in the body affects the extracellular volume, which in turn influences
blood pressure
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
. Therefore, the effects of aldosterone in sodium retention are important for the regulation of blood pressure.
;Glucocorticoids
Cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
is the main
glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
in humans. In species that do not create cortisol, this role is played by
corticosterone
Corticosterone, also known as 17-deoxycortisol and 11β,21-dihydroxyprogesterone, is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands. It is of minor importance in humans, except in the very rare ...
instead. Glucocorticoids have many effects on
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
. As their name suggests, they increase the circulating level of
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
. This is the result of an increase in the mobilization of
amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
from protein and the stimulation of
synthesis of glucose from these amino acids in the liver. In addition, they increase the levels of
free fatty acids
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
, which cells can use as an alternative to glucose to obtain energy. Glucocorticoids also have effects unrelated to the regulation of blood sugar levels, including the suppression of the immune system and a potent
anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...
effect. Cortisol reduces the capacity of
osteoblast
Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...
s to produce new bone tissue and decreases the absorption of calcium in the
gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
.
The adrenal gland secretes a basal level of cortisol but can also produce bursts of the hormone in response to
adrenocorticotropic hormone
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...
(ACTH) from the
anterior pituitary
A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...
. Cortisol is not evenly released during the day – its concentrations in the blood are highest in the early morning and lowest in the evening as a result of the
circadian rhythm
A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., Endogeny (biology), endogeno ...
of ACTH secretion.
Cortisone
Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug; it is not synthesized in the adrenal glands. Cortisol is converted by the action of the enzy ...
is an inactive product of the action of the enzyme
11β-HSD on cortisol. The reaction catalyzed by 11β-HSD is reversible, which means that it can turn administered cortisone into cortisol, the biologically active hormone.
;Formation
![Adrenal Steroids Pathways](https://upload.wikimedia.org/wikipedia/commons/f/f8/Adrenal_Steroids_Pathways.svg)
All
corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
hormones share
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
as a common precursor. Therefore, the first step in
steroidogenesis
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
is cholesterol uptake or synthesis. Cells that produce steroid hormones can acquire cholesterol through two paths. The main source is through dietary cholesterol transported via the blood as
cholesterol esters
file:Cholesterol oleate.svg, 300px, Cholesterol oleate, a member of the cholesteryl ester family
Cholesteryl ester, a dietary lipid, is an ester of cholesterol. The ester bond is formed between the carboxylate group of a fatty acid and the hydroxyl ...
within
low density lipoprotein
Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall density ...
s (LDL). LDL enters the cells through
receptor-mediated endocytosis
Receptor-mediated endocytosis (RME), also called clathrin-mediated endocytosis, is a process by which cells absorb metabolites, hormones, proteins – and in some cases viruses – by the inward budding of the plasma membrane (invagination). Thi ...
. The other source of cholesterol is synthesis in the cell's
endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
. Synthesis can compensate when LDL levels are abnormally low.
In the
lysosome
A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prot ...
, cholesterol esters are converted to free cholesterol, which is then used for steroidogenesis or stored in the cell.
The initial part of conversion of cholesterol into steroid hormones involves a number of enzymes of the
cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
family that are located in the inner membrane of
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
. Transport of cholesterol from the outer to the inner membrane is facilitated by
steroidogenic acute regulatory protein
The steroidogenic acute regulatory protein, commonly referred to as StAR (STARD1), is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones. It is p ...
and is the rate-limiting step of steroid synthesis.
The layers of the adrenal gland differ by function, with each layer having distinct enzymes that produce different hormones from a common precursor.
[ The first enzymatic step in the production of all steroid hormones is cleavage of the cholesterol side chain, a reaction that forms ]pregnenolone
Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/ metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineraloc ...
as a product and is catalyzed by the enzyme P450scc
Cholesterol side-chain cleavage enzyme is commonly referred to as P450scc, where "scc" is an acronym for side-chain cleavage. P450scc is a mitochondrial enzyme that catalyzes conversion of cholesterol to pregnenolone. This is the first reactio ...
, also known as ''cholesterol desmolase''. After the production of pregnenolone, specific enzymes of each cortical layer further modify it. Enzymes involved in this process include both mitochondrial and microsomal
In cell biology, microsomes are heterogeneous vesicle-like artifacts (~20-200 nm diameter) re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, liv ...
P450s and hydroxysteroid dehydrogenase
Hydroxysteroid dehydrogenases (HSDs) are a group of alcohol oxidoreductases that catalyze the dehydrogenation of hydroxysteroids. These enzymes also catalyze the reverse reaction, acting as ketosteroid reductases (KSRs).
There are four types, cl ...
s. Usually a number of intermediate steps in which pregnenolone is modified several times are required to form the functional hormones. Enzymes that catalyze reactions in these metabolic pathways are involved in a number of endocrine diseases. For example, the most common form of congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex. ...
develops as a result of deficiency of 21-hydroxylase
Steroid 21-hydroxylase (also known as steroid 21-monooxygenase, cytochrome P450C21, 21α-hydroxylase and less commonly 21β-hydroxylase) is an enzyme that hydroxylates steroids at the C21 position and is involved in biosynthesis of aldosterone a ...
, an enzyme involved in an intermediate step of cortisol production.
;Regulation
Glucocorticoids are under the regulatory influence of the hypothalamus-pituitary-adrenal (HPA) axis. Glucocorticoid synthesis is stimulated by adrenocorticotropic hormone
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...
(ACTH), a hormone released into the bloodstream by the anterior pituitary
A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...
. In turn, production of ACTH is stimulated by the presence of corticotropin-releasing hormone
Corticotropin-releasing hormone (CRH) (also known as corticotropin-releasing factor (CRF) or corticoliberin; corticotropin may also be spelled corticotrophin) is a peptide hormone involved in stress (biology), stress responses. It is a releasing ...
(CRH), which is released by neurons of the hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
. ACTH acts on the adrenal cells first by increasing the levels of StAR within the cells, and then of all steroidogenic P450 enzymes. The HPA axis is an example of a negative feedback system, in which cortisol itself acts as a direct inhibitor of both CRH and ACTH synthesis. The HPA axis also interacts with the immune system through increased secretion of ACTH at the presence of certain molecules of the inflammatory response
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...
.
Mineralocorticoid secretion is regulated mainly by the renin–angiotensin–aldosterone system (RAAS), the concentration of potassium
Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
, and to a lesser extent the concentration of ACTH. Sensors of blood pressure in the juxtaglomerular apparatus
The juxtaglomerular apparatus (also known as the juxtaglomerular complex) is a structure in the kidney that regulates the function of each nephron, the functional units of the kidney. The juxtaglomerular apparatus is named because it is next to ...
of the kidneys release the enzyme renin
Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the r ...
into the blood, which starts a cascade of reactions that lead to formation of angiotensin II
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adre ...
. Angiotensin receptor
The angiotensin II receptors, (ATR1) and (ATR2), are a class of G protein-coupled receptors with angiotensin II as their ligands. They are important in the renin–angiotensin system: they are responsible for the signal transduction of the vaso ...
s in cells of the zona glomerulosa recognize the substance, and upon binding they stimulate the release of aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
.
Androgens
Cells in zona reticularis
The zona reticularis (sometimes, reticulate zone) is the innermost layer of the adrenal cortex, lying deep to the zona fasciculata and superficial to the adrenal medulla. The cells are arranged cords that project in different directions giving a n ...
of the adrenal glands produce male sex hormones, or androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
s, the most important of which is DHEA
Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It functio ...
. In general, these hormones do not have an overall effect in the male body, and are converted to more potent androgens such as testosterone
Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
and DHT or to estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
s (female sex hormones) in the gonad
A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...
s, acting in this way as a metabolic intermediate
Metabolic intermediates are molecules that are the precursors or metabolites of biologically significant molecules.
Although these intermediates are of relatively minor direct importance to cellular function, they can play important roles in the a ...
.
Catecholamines
Primarily referred to in the United States as epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
and norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
, adrenaline
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
and noradrenaline
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
are catecholamine
A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine.
Catechol can be either a free molecule or a subst ...
s, water-soluble compounds that have a structure made of a catechol
Catechol ( or ), also known as pyrocatechol or 1,2-dihydroxybenzene, is a toxic organic compound with the molecular formula . It is the ''ortho'' isomer of the three isomeric benzenediols. This colorless compound occurs naturally in trace amoun ...
group and an amine group
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such a ...
. The adrenal glands are responsible for most of the adrenaline that circulates in the body, but only for a small amount of circulating noradrenaline. These hormones are released by the adrenal medulla, which contains a dense network of blood vessels. Adrenaline and noradrenaline act by interacting with adrenoreceptor
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...
s throughout the body, with effects that include an increase in blood pressure and heart rate. Actions of adrenaline and noradrenaline are responsible for the fight or flight response
The fight-or-flight or the fight-flight-or-freeze response (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first des ...
, characterised by a quickening of breathing and heart rate, an increase in blood pressure, and constriction of blood vessels in many parts of the body.
;Formation
Catecholamines are produced in chromaffin cells in the medulla of the adrenal gland, from tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
, a non-essential amino acid derived from food or produced from phenylalanine
Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...
in the liver. The enzyme tyrosine hydroxylase
Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA). It does so using molecular oxygen (O2), as well as iron (Fe2+) and t ...
converts tyrosine to L-DOPA
-DOPA, also known as levodopa and -3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA ...
in the first step of catecholamine synthesis. L-DOPA is then converted to dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
before it can be turned into noradrenaline. In the cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
, noradrenaline is converted to epinephrine by the enzyme phenylethanolamine N-methyltransferase
Phenylethanolamine ''N''-methyltransferase (PNMT) is an enzyme found primarily in the adrenal medulla that converts norepinephrine (noradrenaline) to epinephrine (adrenaline). It is also expressed in small groups of neurons in the human brain and ...
(PNMT) and stored in granules. Glucocorticoids produced in the adrenal cortex stimulate the synthesis of catecholamines by increasing the levels of tyrosine hydroxylase and PNMT.
Catecholamine release is stimulated by the activation of the sympathetic nervous system
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...
. Splanchnic nerves
The splanchnic nerves are paired visceral nerves (nerves that contribute to the innervation of the viscera, innervation of the internal organs), carrying fibers of the autonomic nervous system (visceral efferent fibers) as well as sensory fibers fr ...
of the sympathetic nervous system
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...
innervate the medulla of the adrenal gland. When activated, it evokes the release of catecholamines from the storage granules by stimulating the opening of calcium channel
A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels.
Comparison tables
The following tables e ...
s in the cell membrane.
Gene and protein expression
The human genome
The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the n ...
includes approximately 20,000 protein coding genes and 70% of these genes are expressed in the normal adult adrenal glands. Only some 250 genes are more specifically expressed in the adrenal glands compared to other organs and tissues. The adrenal-gland-specific genes with the highest level of expression include members of the cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
superfamily of enzymes. Corresponding proteins are expressed in the different compartments of the adrenal gland, such as CYP11A1
Cholesterol side-chain cleavage enzyme is commonly referred to as P450scc, where "scc" is an acronym for side-chain cleavage. P450scc is a mitochondrial enzyme that catalyzes conversion of cholesterol to pregnenolone. This is the first reactio ...
, HSD3B2
HSD3B2 is a human gene that encodes for 3beta-hydroxysteroid dehydrogenase/delta(5)-delta(4)isomerase type II or hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2. It is expressed principally in steroidogenic tissues ...
and FDX1
Adrenal ferredoxin (also adrenodoxin (ADX), adrenodoxin, mitochondrial, hepatoredoxin, ferredoxin-1 (FDX1)) is a protein that in humans is encoded by the ''FDX1'' gene. In addition to the expressed gene at this chromosomal locus (11q22), there a ...
involved in steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Wi ...
synthesis and expressed in cortical cell layers, and PNMT
Phenylethanolamine ''N''-methyltransferase (PNMT) is an enzyme found primarily in the adrenal medulla that converts norepinephrine (noradrenaline) to epinephrine (adrenaline). It is also expressed in small groups of neurons in the human brain and ...
and DBH involved in noradrenaline
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
and adrenaline
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
synthesis and expressed in the medulla.
Development
The adrenal glands are composed of two heterogenous types of tissue. In the center is the adrenal medulla
The adrenal medulla ( la, medulla glandulae suprarenalis) is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cel ...
, which produces adrenaline
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
and noradrenaline
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
and releases them into the bloodstream, as part of the sympathetic nervous system
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...
. Surrounding the medulla is the cortex
Cortex or cortical may refer to:
Biology
* Cortex (anatomy), the outermost layer of an organ
** Cerebral cortex, the outer layer of the vertebrate cerebrum, part of which is the ''forebrain''
*** Motor cortex, the regions of the cerebral cortex i ...
, which produces a variety of steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Wi ...
s. These tissues come from different embryological
Embryology (from Greek ἔμβρυον, ''embryon'', "the unborn, embryo"; and -λογία, ''-logia'') is the branch of animal biology that studies the prenatal development of gametes (sex cells), fertilization, and development of embryos and ...
precursors and have distinct prenatal development
Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal devel ...
paths. The cortex of the adrenal gland is derived from mesoderm
The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...
, whereas the medulla is derived from the neural crest
Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...
, which is of ectoderm
The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from t ...
al origin.
The adrenal glands in a newborn baby are much larger as a proportion of the body size than in an adult. For example, at age three months the glands are four times the size of the kidneys. The size of the glands decreases relatively after birth, mainly because of shrinkage of the cortex. The cortex, which almost completely disappears by age 1, develops again from age 4–5. The glands weigh about 1 g at birth and develop to an adult weight of about 4 grams each. In a fetus the glands are first detectable after the sixth week of development.[
]
Cortex
Adrenal cortex tissue is derived from the intermediate mesoderm
Intermediate mesoderm or intermediate mesenchyme is a narrow section of the mesoderm (one of the three primary germ layers) located between the paraxial mesoderm and the lateral plate of the developing embryo. The intermediate mesoderm develops i ...
. It first appears 33 days after fertilisation
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
, shows steroid hormone production capabilities by the eighth week and undergoes rapid growth during the first trimester of pregnancy. The fetal adrenal cortex is different from its adult counterpart, as it is composed of two distinct zones: the inner "fetal" zone, which carries most of the hormone-producing activity, and the outer "definitive" zone, which is in a proliferative phase. The fetal zone produces large amounts of adrenal androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
s (male sex hormones) that are used by the placenta
The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
for estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
biosynthesis. Cortical development of the adrenal gland is regulated mostly by ACTH
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important co ...
, a hormone produced by the pituitary gland
In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...
that stimulates cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
synthesis. During midgestation, the fetal zone occupies most of the cortical volume and produces 100–200 mg/day of DHEA-S
Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroep ...
, an androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
and precursor of both androgens and estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
s (female sex hormones). Adrenal hormones, especially glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s such as cortisol, are essential for prenatal development of organs, particularly for the maturation of the lung
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s. The adrenal gland decreases in size after birth because of the rapid disappearance of the fetal zone, with a corresponding decrease in androgen secretion.
Adrenarche
During early childhood androgen synthesis and secretion remain low, but several years before puberty (from 6–8 years of age) changes occur in both anatomical and functional aspects of cortical androgen production that lead to increased secretion of the steroids DHEA
Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It functio ...
and DHEA-S
Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroep ...
. These changes are part of a process called adrenarche
Adrenarche is an early stage in sexual maturation that happens in some higher primates and in humans, typically peaks at around 20 years of age, and is involved in the development of pubic hair, body odor, skin oiliness, axillary hair, sexual ...
, which has only been described in humans and some other primates. Adrenarche is independent of ACTH
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important co ...
or gonadotropin
Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/ chorioni ...
s and correlates with a progressive thickening of the zona reticularis
The zona reticularis (sometimes, reticulate zone) is the innermost layer of the adrenal cortex, lying deep to the zona fasciculata and superficial to the adrenal medulla. The cells are arranged cords that project in different directions giving a n ...
layer of the cortex. Functionally, adrenarche provides a source of androgens for the development of axillary and pubic hair before the beginning of puberty.
Medulla
The adrenal medulla is derived from neural crest cells
Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, Per ...
, which come from the ectoderm
The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from t ...
layer of the embryo
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
. These cells migrate
Migration, migratory, or migrate may refer to: Human migration
* Human migration, physical movement by humans from one region to another
** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
from their initial position and aggregate in the vicinity of the dorsal aorta
The dorsal aortae are paired (left and right) embryological vessels which progress to form the descending aorta. The paired dorsal aortae arise from aortic arches that in turn arise from the aortic sac.
The primary dorsal aorta is located deep t ...
, a primitive blood vessel, which activates the differentiation of these cells through the release of proteins known as BMPs. These cells then undergo a second migration from the dorsal aorta to form the adrenal medulla and other organs of the sympathetic nervous system
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...
. Cells of the adrenal medulla are called chromaffin cells
Chromaffin cells, also called pheochromocytes (or phaeochromocytes), are neuroendocrine cells found mostly in the medulla of the adrenal glands in mammals. These cells serve a variety of functions such as serving as a response to stress, monitori ...
because they contain granules that stain with chromium
Chromium is a chemical element with the symbol Cr and atomic number 24. It is the first element in group 6. It is a steely-grey, lustrous, hard, and brittle transition metal.
Chromium metal is valued for its high corrosion resistance and hardne ...
salts, a characteristic not present in all sympathetic organs. Glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s produced in the adrenal cortex were once thought to be responsible for the differentiation of chromaffin cells. More recent research suggests that BMP-4
Bone morphogenetic protein 4 is a protein that in humans is encoded by ''BMP4'' gene. BMP4 is found on chromosome 14q22-q23.
BMP4 is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfam ...
secreted in adrenal tissue is the main responsible for this, and that glucocorticoids only play a role in the subsequent development of the cells.
Clinical significance
The normal function of the adrenal gland may be impaired by conditions such as infections, tumors, genetic disorders and autoimmune disease
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
s, or as a side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
of medical therapy. These disorders affect the gland either directly (as with infections or autoimmune diseases) or as a result of the dysregulation of hormone production (as in some types of Cushing's syndrome
Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, ...
) leading to an excess or insufficiency of adrenal hormones and the related symptoms.
Corticosteroid overproduction
Cushing's syndrome
Cushing's syndrome
Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, ...
is the manifestation of glucocorticoid excess. It can be the result of a prolonged treatment with glucocorticoids or be caused by an underlying disease which produces alterations in the HPA axis HPA may refer to:
Organizations
* Harry Potter Alliance, a charity
* Halifax Port Authority, Canada
* Hamburg Port Authority, Germany
* Hawaii Preparatory Academy, a school in Hawaii, US
* Health Protection Agency, UK
* Heerespersonalamt, the Ger ...
or the production of cortisol. Causes can be further classified into ACTH
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important co ...
-dependent or ACTH-independent. The most common cause of endogenous
Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell.
In contrast, exogenous substances and processes are those that originate from outside of an organism.
For example, es ...
Cushing's syndrome is a pituitary adenoma
Pituitary adenomas are tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas.[hirsutism
Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...]
), osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
, depression, and most distinctively, stretch marks
Stretch marks, also known as striae () or striae distensae, are a form of scarring on the skin with an off-color hue. Over time they may diminish, but will not disappear completely. Striae are caused by tearing of the dermis during periods of r ...
in the skin, caused by its progressive thinning.
Primary aldosteronism
When the zona glomerulosa produces excess aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
, the result is primary aldosteronism
Primary aldosteronism (PA)'','' also known as primary hyperaldosteronism or Conn's syndrome, refers to the excess production of the hormone aldosterone from the adrenal glands, resulting in low renin levels and high blood pressure. This abnormalit ...
. Causes for this condition are bilateral hyperplasia
Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferati ...
(excessive tissue growth) of the glands, or aldosterone-producing adenoma
An adenoma is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adenom ...
s (a condition called Conn's syndrome
Primary aldosteronism (PA)'','' also known as primary hyperaldosteronism or Conn's syndrome, refers to the excess production of the hormone aldosterone from the adrenal glands, resulting in low renin levels and high blood pressure. This abnormalit ...
). Primary aldosteronism produces hypertension and electrolyte
An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon dis ...
imbalance, increasing potassium
Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
depletion sodium retention.
Adrenal insufficiency
Adrenal insufficiency (the deficiency of glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s) occurs in about 5 in 10,000 in the general population. Diseases classified as ''primary adrenal insufficiency'' (including Addison's disease
Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal ...
and genetic causes) directly affect the adrenal cortex. If a problem that affects the hypothalamic-pituitary-adrenal axis arises outside the gland, it is a ''secondary adrenal insufficiency''.
Addison's disease
Addison's disease refers to primary hypoadrenalism, which is a deficiency in glucocorticoid and mineralocorticoid production by the adrenal gland. In the Western world, Addison's disease is most commonly an autoimmune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...
condition, in which the body produces antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
against cells of the adrenal cortex. Worldwide, the disease is more frequently caused by infection, especially from tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
. A distinctive feature of Addison's disease is hyperpigmentation
Hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin.
Causes
Hyperpigmentation can be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris.James, William; Ber ...
of the skin, which presents with other nonspecific symptoms such as fatigue.
A complication seen in untreated Addison's disease and other types of primary adrenal insufficiency is the adrenal crisis, a medical emergency
A medical emergency is an acute injury or illness that poses an immediate risk to a person's life or long-term health, sometimes referred to as a situation risking "life or limb". These emergencies may require assistance from another, qualified p ...
in which low glucocorticoid and mineralocorticoid levels result in hypovolemic shock
Hypovolemic shock is a form of shock caused by severe hypovolemia (insufficient blood volume or extracellular fluid in the body). It could be the result of severe dehydration through a variety of mechanisms or blood loss. Hypovolemic shock is a ...
and symptoms such as vomiting and fever. An adrenal crisis can progressively lead to stupor
Stupor is the lack of critical mental function and a level of consciousness, in which an affected person is almost entirely unresponsive and responds only to intense stimuli such as pain. The word derives from the Latin '' stupor'' ("numbness, inse ...
and coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
. The management of adrenal crises includes the application of hydrocortisone
Hydrocortisone is the name for the hormone cortisol when supplied as a medication. Uses include conditions such as adrenocortical insufficiency, adrenogenital syndrome, high blood calcium, thyroiditis, rheumatoid arthritis, dermatitis, asthma, ...
injections.
Secondary adrenal insufficiency
In secondary adrenal insufficiency, a dysfunction of the hypothalamic-pituitary-adrenal axis leads to decreased stimulation of the adrenal cortex. Apart from suppression of the axis by glucocorticoid therapy, the most common cause of secondary adrenal insufficiency are tumors that affect the production of adrenocorticotropic hormone
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...
(ACTH) by the pituitary gland
In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...
. This type of adrenal insufficiency usually does not affect the production of mineralocorticoid
Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary mi ...
s, which are under regulation of the renin–angiotensin system
The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance.
When renal blood flow is reduced, juxt ...
instead.
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex. ...
is a congenital disease
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can r ...
in which mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s of enzymes that produce steroid hormones result in a glucocorticoid deficiency and malfunction of the negative feedback loop of the HPA axis HPA may refer to:
Organizations
* Harry Potter Alliance, a charity
* Halifax Port Authority, Canada
* Hamburg Port Authority, Germany
* Hawaii Preparatory Academy, a school in Hawaii, US
* Health Protection Agency, UK
* Heerespersonalamt, the Ger ...
. In the HPA axis, cortisol (a glucocorticoid) inhibits the release of CRH CRH may refer to:
* Calibre radius head, a traditional British ordnance term for a concept in ballistic projectile design
* Celtic Resources Holdings, an Irish mining company
* China Railway High-speed, a high-speed railway service operated by Chin ...
and ACTH
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important co ...
, hormones that in turn stimulate corticosteroid synthesis. As cortisol cannot be synthesized, these hormones are released in high quantities and stimulate production of other adrenal steroids instead. The most common form of congenital adrenal hyperplasia is due to 21-hydroxylase
Steroid 21-hydroxylase (also known as steroid 21-monooxygenase, cytochrome P450C21, 21α-hydroxylase and less commonly 21β-hydroxylase) is an enzyme that hydroxylates steroids at the C21 position and is involved in biosynthesis of aldosterone a ...
deficiency. 21-hydroxylase is necessary for production of both mineralocorticoids and glucocorticoids, but not androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
s. Therefore, ACTH stimulation of the adrenal cortex induces the release of excessive amounts of adrenal androgen Adrenal steroids are steroids that are derived from the adrenal glands. They include corticosteroids, which consist of glucocorticoids like cortisol and mineralocorticoids like aldosterone, adrenal androgens like dehydroepiandrosterone (DHEA), DHEA ...
s, which can lead to the development of ambiguous genitalia
A sex organ (or reproductive organ) is any part of an animal or plant that is involved in sexual reproduction. The reproductive organs together constitute the reproductive system. In animals, the testis in the male, and the ovary in the female, a ...
and secondary sex characteristic
Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a sp ...
s.
Adrenal tumors
Adrenal tumors are commonly found as incidentaloma
In medical or research imaging, an incidental imaging finding (also called an incidentaloma) is an unanticipated finding which is not related to the original diagnostic inquiry. As with other types of incidental medical findings, they may represen ...
s, unexpected asymptomatic
In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered asy ...
tumors found during medical imaging
Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...
. They are seen in around 3.4% of CT scans, and in most cases they are benign adenoma
An adenoma is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adenom ...
s. Adrenal carcinoma
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex whic ...
s are very rare, with an incidence of 1 case per million per year.
Pheochromocytomas
Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred ...
are tumors of the adrenal medulla that arise from chromaffin cell
Chromaffin cells, also called pheochromocytes (or phaeochromocytes), are neuroendocrine cells found mostly in the medulla of the adrenal glands in mammals. These cells serve a variety of functions such as serving as a response to stress, monitor ...
s. They can produce a variety of nonspecific symptoms, which include headaches, sweating, anxiety and palpitation
Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart.
Symptoms include a rapi ...
s. Common signs include hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
and tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
. Surgery, especially adrenal laparoscopy
Laparoscopy () is an operation performed in the abdomen or pelvis using small incisions (usually 0.5–1.5 cm) with the aid of a camera. The laparoscope aids diagnosis or therapeutic interventions with a few small cuts in the abdomen.Medli ...
, is the most common treatment for small pheochromocytomas.
History
Bartolomeo Eustachi
Bartolomeo Eustachi (c. 1500–1510 – 27 August 1574), also known by his Latin name of Bartholomaeus Eustachius (), was an Italian anatomist and one of the founders of the science of human anatomy.
Biography
Bartolomeo Eustachio (known as Eu ...
, an Italian anatomist, is credited with the first description of the adrenal glands in 1563–4. However, these publications were part of the papal library and did not receive public attention, which was first received with Caspar Bartholin the Elder
Caspar Bartholin the Elder (; 12 February 1585 – 13 July 1629) was a Danish physician, scientist and theologian.
Biography
Caspar Berthelsen Bartholin was born at Malmö, Malmø, Denmark (modern Sweden). His precocity was extraordinary; at thr ...
's illustrations in 1611.
The adrenal glands are named for their location relative to the kidneys. The term "adrenal" comes from Latin
Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
'' ad'', "near", and ''ren Ren or REN may refer to:
Abbreviations
* Orenburg Tsentralny Airport, IATA code REN, civil airport in Russia
* Redes Energéticas Nacionais (REN), Portuguese company
* Renanthera, abbreviated as Ren, orchid genus
* Ringer equivalence number ( ...
'', "kidney". Similarly, "suprarenal", as termed by Jean Riolan the Younger
Jean Riolan (the Younger) (15 February 1577 or 1580 – 19 February 1657) was a French anatomist who was an influential member of the Medical Faculty of Paris. His father, Jean Riolan (the Elder) (1539–1605) was also a noted French anatomist. Ri ...
in 1629, is derived from the Latin
Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
''supra
Supra may refer to:
* Supra (feast), an important part of Georgian social culture
*Toyota Supra, a sports car/grand tourer produced from 1978 to 2002, and then since 2019
* Supra (footwear brand)
*Sydney University Postgraduate Representative Asso ...
'', "above", and ''ren'', "kidney", as well. The suprarenal nature of the glands was not truly accepted until the 19th century, as anatomists clarified the ductless nature of the glands and their likely secretory role – prior to this, there was some debate as to whether the glands were indeed suprarenal or part of the kidney.
One of the most recognized works on the adrenal glands came in 1855 with the publication of ''On the Constitutional and Local Effects of Disease of the Suprarenal Capsule'', by the English physician Thomas Addison
Thomas J Addison (April 179329 June 1860) was an English physician, chef, and scientist. He is traditionally regarded as one of the "great men" of Guy's Hospital in London.
Among other pathologies, he discovered Addison's disease (a degenerati ...
. In his monography, Addison described what the French physician George Trousseau would later name Addison's disease
Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal ...
, an eponym still used today for a condition of adrenal insufficiency
Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal gland normally secretes glucocorticoids (primarily cortisol), mineralocorticoids (primarily aldosterone), and androge ...
and its related clinical manifestations. In 1894, English physiologists George Oliver and Edward Schafer studied the action of adrenal extracts and observed their pressor
An antihypotensive agent, also known as a vasopressor agent or simply vasopressor, or pressor, is any substance, whether endogenous or a medication, that tends to raise low blood pressure. Some antihypotensive drugs act as vasoconstrictors to inc ...
effects. In the following decades several physicians experimented with extracts from the adrenal cortex to treat Addison's disease. Edward Calvin Kendall
Edward Calvin Kendall (March 8, 1886 – May 4, 1972) was an American chemist. In 1950, Kendall was awarded the Nobel Prize for Physiology or Medicine along with Swiss chemist Tadeusz Reichstein and Mayo Clinic physician Philip S. Hench, for the ...
, Philip Hench
Philip Showalter Hench (February 28, 1896 – March 30, 1965) was an American physician. Hench, along with his Mayo Clinic co-worker Edward Calvin Kendall and Swiss chemist Tadeus Reichstein was awarded the Nobel Prize for Physiology or Medicine ...
and Tadeusz Reichstein
Tadeusz Reichstein (20 July 1897 – 1 August 1996) was a Polish-Swiss chemist and the Nobel Prize in Physiology or Medicine laureate (1950), which was awarded for his work on the isolation of cortisone.
Early life
Reichstein was born into a Pol ...
were then awarded the 1950 Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
for their discoveries on the structure and effects of the adrenal hormones.
See also
* Adrenopause
Adrenopause is the decline in secretion and levels of adrenal androgens such as dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) from the zona reticularis of the adrenal glands with age. Levels of adrenal androgens start ...
References
External links
Adrenal gland at the Human Protein Atlas
*
Adrenal gland histology
* – "Adrenal Gland"
*
* – "Posterior Abdominal Wall: The Retroperitoneal Fat and Suprarenal Glands"
from Colorado State University
*
{{DEFAULTSORT:Adrenal Gland
Adrenaline