Aldosterone is the main mineralocorticoid
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). Withi ...
produced by 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 ...
of the
adrenal cortex in the
adrenal gland
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 ...
. It is essential for
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 ...
conservation in the kidney, salivary glands, sweat glands, and colon.
It plays a central role in the
homeostatic
In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
regulation of
blood pressure, plasma
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 ...
(Na
+), and
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 ...
(K
+) levels. It does so primarily by acting on the mineralocorticoid receptors in the
distal 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
collecting duct
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 ...
s of the
nephron
The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ...
.
It influences the reabsorption of sodium and excretion of potassium (from and into the tubular fluids, respectively) of 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 ...
, thereby indirectly influencing
water retention or loss,
blood pressure, and
blood volume.
[Marieb Human Anatomy & Physiology 9th edition, chapter:16, page:629, question number:14] When dysregulated, aldosterone is pathogenic and contributes to the development and progression of
cardiovascular
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
and
kidney disease. Aldosterone has exactly the opposite function of the
atrial natriuretic hormone
Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides (ANP, BNP, and CNP) are a family of hormone/pa ...
secreted by the
heart
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
.
Aldosterone is part of the
renin–angiotensin–aldosterone system. It has a
plasma half-life
Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
of less than 20 minutes. Drugs that interfere with the secretion or action of aldosterone are in use as antihypertensives, like
lisinopril
Lisinopril is a medication of the angiotensin-converting enzyme (ACE) inhibitor and is used to treat high blood pressure, heart failure, and after heart attacks. For high blood pressure it is usually a first-line treatment. It is also used t ...
, which lowers blood pressure by blocking the
angiotensin-converting enzyme (ACE), leading to lower aldosterone secretion. The net effect of these drugs is to reduce sodium and water retention but increase retention of potassium. In other words, these drugs stimulate the excretion of sodium and water in urine, while they block the excretion of potassium.
Another example is
spironolactone
Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood press ...
, a
potassium-sparing diuretic
Potassium-sparing diuretics refers to drugs that cause diuresis without causing potassium loss in the urine. They are typically used as an adjunct in management of hypertension, cirrhosis, and congestive heart failure. The steroidal aldostero ...
of the
steroidal
spirolactone
Spirolactones are a class of functional group in organic chemistry featuring a cyclic ester attached spiro to another ring system. The name is also used to refer to a class of synthetic steroids, called steroid-17α-spirolactones, 17α-spiro ...
group, which interferes with the aldosterone receptor (among others) leading to lower blood pressure by the mechanism described above.
Aldosterone was first isolated by
Sylvia Tait (Simpson) and
Jim Tait
Jim Tait (November 6, 1935 – May 20, 2011) was an American football player, coach, and college athletics administrator. He was head football coach at the University of Richmond from 1974 until 1979, compiling a record of 21–44. In 1975, Richm ...
in 1953; in collaboration with
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 Po ...
.
Biosynthesis
The
corticosteroids are synthesized from
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 ...
within 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 ...
and zona fasciculata of
adrenal cortex. Most
steroidogenic
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 ...
reactions are catalysed by enzymes of the
cytochrome
Cytochromes are redox-active proteins containing a heme, with a central Fe atom at its core, as a cofactor. They are involved in electron transport chain and redox catalysis. They are classified according to the type of heme and its mode of bi ...
P450 family. They are located within the
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 require
adrenodoxin
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 ...
as a cofactor (except
21-hydroxylase and
17α-hydroxylase).
Aldosterone and
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 rar ...
share the first part of their biosynthetic pathways. The last parts are mediated either by the
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 ...
(for aldosterone) or by the
11β-hydroxylase (for corticosterone). These enzymes are nearly identical (they share 11β-hydroxylation and
18-hydroxylation functions), but aldosterone synthase is also able to perform an 18-
oxidation
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
. Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the
adrenal cortex; 11β-hydroxylase is found in 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 ...
and
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 ...
.
![Steroidogenesis](https://upload.wikimedia.org/wikipedia/commons/1/13/Steroidogenesis.svg)
Aldosterone synthase is absent in other sections of the
adrenal gland
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 ...
.
Stimulation
Aldosterone synthesis is stimulated by several factors:
* increase in the plasma concentration of angiotensin III, a metabolite of angiotensin II
* increase in
plasma angiotensin II,
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 c ...
, or
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 ...
levels, which are present in proportion to plasma sodium deficiencies. (The increased potassium level works to regulate aldosterone synthesis by depolarizing the cells in 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 ...
, which opens the
voltage-dependent calcium channel
Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permea ...
s.) The level of angiotensin II is regulated by
angiotensin I
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 a ...
, which is in turn regulated by
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 ...
, a hormone secreted in the kidneys.
* Serum potassium concentrations are the most potent stimulator of aldosterone secretion.
* the
ACTH stimulation test
The ACTH test (also called the cosyntropin, tetracosactide, or Synacthen test) is a medical test usually requested and interpreted by endocrinologists to assess the functioning of the adrenal glands' stress response by measuring the adrenal respon ...
, which is sometimes used to stimulate the production of aldosterone along with
cortisol to determine whether primary or secondary
adrenal insufficiency is present. However, ACTH has only a minor role in regulating aldosterone production; with hypopituitarism there is no atrophy of the zona glomerulosa.
* plasma
acidosis
Acidosis is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma.
The term ''acidemia'' describes ...
* the
stretch receptors located in the
atria of the heart. If decreased blood pressure is detected, the adrenal gland is stimulated by these stretch receptors to release aldosterone, which increases sodium reabsorption from the urine, sweat, and the gut. This causes increased osmolarity in the extracellular fluid, which will eventually return blood pressure toward normal.
* adrenoglomerulotropin, a
lipid factor
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...
, obtained from pineal extracts. It selectively stimulates secretion of aldosterone.
The secretion of aldosterone has a
diurnal rhythm.
Biological function
Aldosterone is the primary of several endogenous members of the class 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 ...
s in humans.
Deoxycorticosterone Deoxycorticosterone (DOC), or desoxycorticosterone, may refer to:
* 11-Deoxycorticosterone (21-hydroxyprogesterone)
* 21-Deoxycorticosterone (11β-hydroxyprogesterone)
See also
* Deoxycortisol
* Deoxycortisone
* 11-Hydroxyprogesterone
{{Che ...
is another important member of this class. Aldosterone tends to promote Na
+ and water retention, and lower plasma K
+ concentration by the following mechanisms:
# Acting on the nuclear
mineralocorticoid receptor
The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the ''NR3C2'' gene that is located on chromosome 4q31 ...
s (MR) within the principal cells of the
distal 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 ...
and the
collecting duct
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 ...
of the kidney nephron, it upregulates and activates the
basolateral
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (th ...
Na+/K+ pumps, which pumps three sodium ions out of the cell, into the interstitial fluid and two potassium ions into the cell from the interstitial fluid. This creates a concentration gradient which results in reabsorption of sodium (Na
+) ions and water (which follows sodium) into the blood, and secreting potassium (K
+) ions into the urine (lumen of collecting duct).
# Aldosterone upregulates epithelial sodium channels (
ENaC
The epithelial sodium channel (ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (). It is assembled as a heterotrimer composed of three homologous subunits α ...
s) in the
collecting duct
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 ...
and the colon, increasing apical membrane permeability for Na
+ and thus absorption.
# Cl
− is reabsorbed in conjunction with sodium cations to maintain the system's electrochemical balance.
# Aldosterone stimulates the secretion of K
+ into the tubular lumen.
# Aldosterone stimulates Na
+ and water reabsorption from the gut, salivary and sweat glands in exchange for K
+.
# Aldosterone stimulates secretion of H
+ via the H+/ATPase in the
intercalated cells of the cortical collecting tubules
# Aldosterone upregulates expression of
NCC in the distal convoluted tubule chronically and its activity acutely.
Aldosterone is responsible for the reabsorption of about 2% of filtered sodium in the kidneys, which is nearly equal to the entire sodium content in human blood under normal
glomerular filtration rate
Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood p ...
s.
Aldosterone, probably acting through mineralocorticoid receptors, may positively influence neurogenesis in the
dentate gyrus
The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute t ...
.
Mineralocorticoid receptors
Steroid receptor
Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors (typically cytoplasmic or nuclear) and initiate signal transduction for steroid hormones which ...
s are
intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
. The aldosterone
mineralocorticoid receptor
The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the ''NR3C2'' gene that is located on chromosome 4q31 ...
(MR) complex binds on the DNA to specific
hormone response element Response elements are short sequences of DNA within a gene promoter or enhancer region that are able to bind specific transcription factors and regulate transcription of genes.
Under conditions of stress, a transcription activator protein binds ...
, which leads to gene specific
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
.
Some of the transcribed genes are crucial for transepithelial sodium transport, including the three
subunits of the
epithelial sodium channel (ENaC), the
Na+/K+ pumps and their regulatory proteins
serum and glucocorticoid-induced kinase
Serine/threonine-protein kinases SGK represent a kinase subfamily with Homology (biology)#Orthology, orthologs found across animal clades and in yeast (comparTreefam family TF320906. In most vertebrates, including humans, there are three isoform ...
, and
channel-inducing factor, respectively.
The MR is stimulated by both aldosterone and cortisol, but a mechanism protects the body from excess aldosterone receptor stimulation by glucocorticoids (such as cortisol), which happen to be present at much higher concentrations than mineralocorticoids in the healthy individual. The mechanism consists of an enzyme called
11 β-hydroxysteroid dehydrogenase (11β-HSD). This enzyme co-localizes with intracellular adrenal steroid receptors and converts cortisol into cortisone, a relatively inactive metabolite with little affinity for the MR.
Liquorice, which contains
glycyrrhetinic acid
Enoxolone (INN, BAN; also known as glycyrrhetinic acid or glycyrrhetic acid) is a pentacyclic triterpenoid derivative of the beta-amyrin type obtained from the hydrolysis of glycyrrhizic acid, which was obtained from the herb liquorice. It is u ...
, can inhibit 11β-HSD and lead to a mineralocorticoid excess syndrome.
Control of aldosterone release from the adrenal cortex
Major regulators
The role 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, ...
Angiotensin is involved in regulating aldosterone and is the core regulation. Angiotensin II acts synergistically with potassium, and the potassium feedback is virtually inoperative when no angiotensin II is present. A small portion of the regulation resulting from angiotensin II must take place indirectly from decreased blood flow through the liver due to constriction of capillaries. When the blood flow decreases so does the destruction of aldosterone by liver enzymes.
Although sustained production of aldosterone requires persistent
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
entry through low-voltage-activated
Ca2+ channels, isolated zona glomerulosa cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit
Ca2+ channels entry.
However, mouse zona glomerulosa cells within adrenal slices spontaneously generate membrane potential oscillations of low periodicity; this innate electrical excitability of zona glomerulosa cells provides a platform for the production of a recurrent Ca
2+ channels signal that can be controlled by
angiotensin II 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 ...
, the 2 major regulators of aldosterone production.
Voltage-gated Ca2+ channels have been detected in the zona glomerulosa of the human adrenal, which suggests that
Ca2+ channel blockers may directly influence the adrenocortical biosynthesis of aldosterone in vivo.
The plasma 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 ...
The amount of plasma renin secreted is an indirect function of the serum potassium as probably determined by sensors in the carotid artery.
Adrenocorticotropic hormone
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 pituitary peptide, also has some stimulating effect on aldosterone, probably by stimulating the formation of
deoxycorticosterone Deoxycorticosterone (DOC), or desoxycorticosterone, may refer to:
* 11-Deoxycorticosterone (21-hydroxyprogesterone)
* 21-Deoxycorticosterone (11β-hydroxyprogesterone)
See also
* Deoxycortisol
* Deoxycortisone
* 11-Hydroxyprogesterone
{{Che ...
, a precursor of aldosterone. Aldosterone is increased by blood loss, pregnancy,
and possibly by further circumstances such as physical exertion, endotoxin shock, and burns.
Miscellaneous regulators
The role of sympathetic nerves
The aldosterone production is also affected to one extent or another by nervous control, which integrates the inverse of carotid artery pressure,
[Gann DS Mills IH Bartter 1960 On the hemodynamic parameter mediating increase in aldosterone secretion in the dog. Fed. Proceedings 19; 605–610.] pain, posture,
and probably emotion (anxiety, fear, and hostility)
(including
surgical stress). Anxiety increases aldosterone,
which must have evolved because of the time delay involved in migration of aldosterone into the cell nucleus. Thus, there is an advantage to an animal's anticipating a future need from interaction with a predator, since too high a serum content of potassium has very adverse effects on nervous transmission.
The role of baroreceptors
Pressure-sensitive
baroreceptors are found in the vessel walls of nearly all large arteries in the thorax and neck, but are particularly plentiful in the sinuses of the carotid arteries and in the arch of the aorta. These specialized receptors are sensitive to changes in mean arterial pressure. An increase in sensed pressure results in an increased rate of firing by the baroreceptors and a negative feedback response, lowering systemic arterial pressure. Aldosterone release causes sodium and water retention, which causes increased blood volume, and a subsequent increase in blood pressure, which is sensed by the baroreceptors. To maintain normal homeostasis these receptors also detect low blood pressure or low blood volume, causing aldosterone to be released. This results in sodium retention in the kidney, leading to water retention and increased blood volume.
The plasma concentration 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 ...
Aldosterone levels vary as an
inverse function
In mathematics, the inverse function of a function (also called the inverse of ) is a function that undoes the operation of . The inverse of exists if and only if is bijective, and if it exists, is denoted by f^ .
For a function f\colon X ...
of sodium intake as sensed via osmotic pressure. The slope of the response of aldosterone to serum potassium is almost independent of sodium intake. Aldosterone is increased at low sodium intakes, but the rate of increase of plasma aldosterone as potassium rises in the serum is not much lower at high sodium intakes than it is at low. Thus, potassium is strongly regulated at all sodium intakes by aldosterone when the supply of potassium is adequate, which it usually is in "primitive" diets.
Aldosterone feedback
Feedback by aldosterone concentration itself is of a nonmorphological character (that is, other than changes in the cells' number or structure) and is poor, so the electrolyte feedbacks predominate, short term.
[
]
Associated clinical conditions
Hyperaldosteronism is abnormally increased levels of aldosterone, while hypoaldosteronism
Hypoaldosteronism is an endocrinological disorder characterized by decreased levels of the hormone aldosterone. Similarly, isolated hypoaldosteronism is the condition of having lowered aldosterone without corresponding changes in cortisol. (T ...
is abnormally decreased levels of aldosterone.
A measurement of aldosterone in blood may be termed a ''plasma aldosterone concentration'' (''PAC''), which may be compared to plasma renin activity
Plasma renin activity (PRA), also known as the renin (active) assay or random plasma renin, is a measure of the activity of the plasma enzyme renin, which plays a major role in the body's regulation of blood pressure, thirst, and urine output. Me ...
(PRA) as an aldosterone-to-renin ratio Aldosterone-to-renin ratio (ARR) is the mass concentration of aldosterone divided by the plasma renin activity or by serum renin concentration in blood. The aldosterone/renin ratio is recommended as screening tool for primary hyperaldosteronism.
...
.
Hyperaldosteronism
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 ...
, also known as ''primary hyperaldosteronism'', is characterized by the overproduction of aldosterone by the adrenal gland
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, when not a result of excessive renin secretion. It leads to arterial 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 ...
(high blood pressure) associated with hypokalemia, usually a diagnostic clue. Secondary hyperaldosteronism
Hyperaldosteronism is a medical condition wherein too much aldosterone is produced by the adrenal glands, which can lead to lowered levels of potassium in the blood (hypokalemia) and increased hydrogen ion excretion (alkalosis).
This cause of min ...
, on the other hand, is due to overactivity 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, ...
.
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 ...
is primary hyperaldosteronism caused by an aldosterone-producing adenoma.
Depending on cause and other factors, hyperaldosteronism can be treated by surgery and/or medically, such as by aldosterone antagonist
An antimineralocorticoid, also known as a mineralocorticoid receptor antagonist (MRA or MCRA) or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is often u ...
s.
The ratio of renin to aldosterone is an effective screening test to screen for primary hyperaldosteronism related to adrenal adenoma
Adrenocortical adenoma is commonly described as a benign neoplasm emerging from the cells that comprise the adrenal cortex. Like most adenomas, the adrenocortical adenoma is considered a benign tumor since the majority of them are non-functioning ...
s. It is the most sensitive serum blood test to differentiate primary from secondary causes of hyperaldosteronism. Blood obtained when the patient has been standing for more than 2 hours are more sensitive than those from when the patient is lying down. Before the test, individuals should not restrict salt and low potassium
Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...
should be corrected before the test because it can suppress aldosterone secretion.
Hypoaldosteronism
An ACTH stimulation test for aldosterone can help in determining the cause of hypoaldosteronism
Hypoaldosteronism is an endocrinological disorder characterized by decreased levels of the hormone aldosterone. Similarly, isolated hypoaldosteronism is the condition of having lowered aldosterone without corresponding changes in cortisol. (T ...
, with a low aldosterone response indicating a primary hypoaldosteronism of the adrenals, while a large response indicating a secondary hypoaldosteronism.
The most common cause of this condition (and related symptoms) is 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 adre ...
; it is typically treated by fludrocortisone
Fludrocortisone, sold under the brand name Florinef, among others, is a corticosteroid used to treat adrenogenital syndrome, postural hypotension, and adrenal insufficiency. In adrenal insufficiency, it is generally taken together with hydroc ...
, which has a much longer persistence (1 day) in the bloodstream.
Additional images
Image:Corticosteroid-biosynthetic-pathway-rat.png, Corticosteroid biosynthetic pathway in rat
Image:Corticosterone.svg, 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 rar ...
References
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Aldehydes
GPER agonists
Mineralocorticoids
Pregnanes
Steroid hormones
Triketones
Enones