Adrenal cortex
Encyclopedia
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Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
, the adrenal cortex mediates the stress response through the production of mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
s and glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
s, including aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
and cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
respectively. It is also a secondary site of androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
synthesis.
Layers
| Layer | Name | Primary product >- | Most superficial cortical layer |
zona glomerulosa Zona glomerulosa The zona glomerulosa of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the adrenal gland's capsule... |
mineralocorticoid Mineralocorticoid Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:... s (e.g., aldosterone Aldosterone Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that... ) >- | Middle cortical layer |
zona fasciculata Zona fasciculata The zona fasciculata constitutes the middle zone of the adrenal cortex, sitting directly beneath the zona glomerulosa. Constituent cells are organized into bundles or "fascicles".... |
glucocorticoid Glucocorticoid Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell... s (e.g., cortisol Cortisol Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,... ) >- | Deepest cortical layer |
zona reticularis Zona reticularis The zona reticularis 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 net-like appearance The zona reticularis is the innermost layer of the adrenal... |
weak androgen Androgen Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors... s (e.g., dehydroepiandrosterone Dehydroepiandrosterone 5-Dehydroepiandrosterone is a 19-carbon endogenous steroid hormone. It is the major secretory steroidal product of the adrenal glands and is also produced by the gonads and the brain. DHEA is the most abundant circulating steroid in humans.... , adrenosterone Adrenosterone Adrenosterone is a steroid hormone with weak androgenic effect. It was first isolated in 1936 from the adrenal cortex by Tadeus Reichstein at the Pharmaceutical Institute in the University of Basel. Originally, adrenosterone was called Reichstein's substance G... ) |
Notably, the reticularis in all animals is not always easily distinguishable and dedicated to androgen synthesis. In rodents, for instance, the reticularis also generates corticosteroids (specifically corticosterone
Corticosterone
Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...
, not cortisol). The two layers are collectively referred to as the fasciculo-reticularis.
Female rodents also exhibit another cortical layer called the "X zone" whose function is not yet clear.
Hormone synthesis
All adrenocortical hormones are synthesized from cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
. Cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
is transported into the adrenal gland. The steps up to this point occur in many steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
-producing tissues. Subsequent steps to generate aldosterone and cortisol, however, primarily occur in the adrenal cortex:
- Progesterone → (hydroxylation at C21) → 11-DeoxycorticosteroneDeoxycorticosterone11-Deoxycorticosterone is a steroid hormone produced by the adrenal gland that possesses mineralocorticoid activity and acts as a precursor to aldosterone. As its names indicate, it can be understood as 21-hydroxy- variant of progesterone or a 11-deoxy- variant of corticosterone...
→ (two further hydroxylations at C11 and C18) → AldosteroneAldosteroneAldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that... - Progesterone → (hydroxylation at C17) → 17-alpha-hydroxyprogesterone → (hydroxylation at C21) → 11-Deoxycortisol → (hydroxylation at C11) → CortisolCortisolCortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
Mineralocorticoids
They are produced in the zona glomerulosaZona glomerulosa
The zona glomerulosa of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the adrenal gland's capsule...
. The primary mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
is aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
. Its secretion is regulated by the oligopeptide
Oligopeptide
An oligopeptide consists of between 2 and 20 amino acids and includes dipeptides, tripeptides, tetrapeptides, pentapeptides, etc.Examples of oligopeptides include:...
angiotensin II (angiotensin II is regulated by angiotensin I, which in turn is regulated by renin
Renin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
). Aldosterone is secreted in response to high extracellular
Extracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
levels, low extracellular sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
levels, and low fluid levels and blood volume. Aldosterone affects metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
in different ways:
- It increases urinaryUrineUrine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
excretion of potassium ions - It increases interstitial levels of sodium ions
- It increases water retention and blood volume
Glucocorticoids
They are produced in the zona fasciculataZona fasciculata
The zona fasciculata constitutes the middle zone of the adrenal cortex, sitting directly beneath the zona glomerulosa. Constituent cells are organized into bundles or "fascicles"....
. The primary glucocorticoid released by the adrenal gland in the human is cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
and corticosterone
Corticosterone
Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...
in many other animals. Its secretion is regulated by the hormone ACTH
Adrenocorticotropic hormone
Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
from the anterior pituitary
Anterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
. Upon binding to its target, cortisol enhances metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
in several ways:
- It stimulates the release of amino acidAmino acidAmino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s from the body - It stimulates lipolysisLipolysisLipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into free fatty acids followed by further degradation into acetyl units by beta oxidation. The process produces Ketones, which are found in large quantities in ketosis, a metabolic state that occurs when the liver...
, the breakdown of fatFatFats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure... - It stimulates gluconeogenesisGluconeogenesisGluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
, the production of glucoseGlucoseGlucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
from newly-released amino acids and lipidLipidLipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s - It increases blood glucose levels in response to stress, by inhibiting glucose uptake into muscle and fat cellsAdipose tissueIn histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
- It strengthens cardiac muscleCardiac muscleCardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
contractions - It increases water retention
- It has anti-inflammatory and anti-allergic effects
Androgens
They are produced in the zona reticularisZona reticularis
The zona reticularis 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 net-like appearance The zona reticularis is the innermost layer of the adrenal...
. The most important androgens include:
- TestosteroneTestosteroneTestosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
: a hormone with a wide variety of effects, ranging from enhancing muscle mass and stimulation of cell growthCell growthThe term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
to the development of the secondary sex characteristicSecondary sex characteristicSecondary sex characteristics are features that distinguish the two sexes of a species, but that are not directly part of the reproductive system. They are believed to be the product of sexual selection for traits which give an individual an advantage over its rivals in courtship and aggressive...
s. - DihydrotestosteroneDihydrotestosteroneDihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
(DHT): a metaboliteMetabolismMetabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
of testosterone, and a more potent androgen than testosterone in that it binds more strongly to androgen receptors. - AndrostenedioneAndrostenedioneAndrostenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.-Synthesis:Androstenedione is the common precursor of male and female sex...
(Andro): an androgenic steroid produced by the testes, adrenal cortex, and ovaries. While androstenedioneAndrostenedioneAndrostenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.-Synthesis:Androstenedione is the common precursor of male and female sex...
s are converted metabolically to testosterone and other androgenAndrogenAndrogen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
s, they are also the parent structure of estroneEstroneEstrone is an estrogenic hormone secreted by the ovary as well as adipose tissue.Estrone is one of several natural estrogens, which also include estriol and estradiol...
. - DehydroepiandrosteroneDehydroepiandrosterone5-Dehydroepiandrosterone is a 19-carbon endogenous steroid hormone. It is the major secretory steroidal product of the adrenal glands and is also produced by the gonads and the brain. DHEA is the most abundant circulating steroid in humans....
(DHEA): It is the primary precursor of natural estrogenEstrogenEstrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
s. DHEA is also called dehydroisoandrosterone or dehydroandrosterone. The reticularis also produces DHEA-sulfate due to the actions of a sulfotransferaseSulfotransferaseSulfotransferases are transferase enzymes that catalyze the transfer of a sulfate group from a donor molecule to an acceptor alcohol or amine. The most common sulfate donor is 3'-phosphoadenosine-5'-phosphosulfate...
, SULT2A1SULT2A1Alcohol sulfotransferase is an enzyme that catalyzes the sulfate conjugation of primary and secondary alcohols including many hormones, neurotransmitters, drugs, and xenobiotic compounds.- Family members :...
.
Pathology
- Adrenal insufficiencyAdrenal insufficiencyAdrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...
(e.g. due to Addison's diseaseAddison's diseaseAddison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
) - Cushing's syndromeCushing's syndromeCushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
- Conn's syndromeConn's syndromePrimary aldosteronism, also known as primary hyperaldosteronism, is characterized by the overproduction of the mineralocorticoid hormone aldosterone by the adrenal glands., when not a result of excessive renin secretion. Aldosterone causes increase in sodium and water retention and potassium...
- Adrenal Virilism