Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release (secretion) of potassium in the
collecting ductsThe collecting duct system of the kidney consists of a series of tubules and ducts that connect the nephrons to the ureter. It participates in electrolyte and fluid balance through reabsorption and excretion, processes regulated by the hormones aldosterone and antidiuretic hormone.There are several...
and
distal convoluted tubuleThe distal convoluted tubule is a portion of kidney nephron between the loop of Henle and the collecting duct system.- Physiology :It is partly responsible for the regulation of potassium, sodium, calcium, and pH...
of the kidneys' functional unit, the
nephronThe renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....
. This increases blood volume and, therefore, increases blood pressure. Drugs that interfere with the secretion or action of aldosterone are in use as antihypertensives. One example is
spironolactoneSpironolactone , commonly referred to as simply spiro, is a diuretic and is used as an antiandrogen.It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called...
, which lowers blood pressure by blocking the aldosterone receptor. Aldosterone is part of the renin-angiotensin system.
Aldosterone is a yellow
steroid hormoneA steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...
(
mineralocorticoidMineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
family) produced by the outer-section (
zona glomerulosaThe zona glomerulosa of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the adrenal gland's capsule...
) of the
adrenal cortexSituated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.-Layers:Notably, the reticularis in...
in the
adrenal glandIn 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...
, and acts on the distal tubules and collecting ducts of the nephron, the functioning unit of the
kidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
to cause the conservation of
sodiumSodium 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...
, secretion of
potassiumPotassium 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...
, increased water retention, and increased
blood pressureBlood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
. The overall effect of aldosterone is to increase reabsorption of ions and water in the kidney.
Its activity is reduced in
Addison's diseaseAddison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
and increased in
Conn'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...
.
It was first isolated by Simpson and Tait in 1953.
Synthesis
The corticosteroids are synthesized from
cholesterolCholesterol 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...
within the
adrenal cortexSituated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.-Layers:Notably, the reticularis in...
. Most steroidogenic reactions are catalysed by enzymes of the
cytochromeCytochromes are, in general, membrane-bound hemoproteins that contain heme groups and carry out electron transport.They are found either as monomeric proteins or as subunits of bigger enzymatic complexes that catalyze redox reactions....
P450 family. They are located within the mitochondria and require adrenodoxin as a cofactor (except
21-hydroxylaseSteroid 21-hydroxylase is a cytochrome P450 enzyme that is involved with the biosynthesis of the steroid hormones aldosterone and cortisol.In humans, 21-Hydroxylase is encoded by the gene CYP21A2.-Names and classification:...
and 17α-hydroxylase).
Aldosterone and
corticosteroneCorticosterone 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...
share the first part of their biosynthetic pathway. The last part is mediated either by the
aldosterone synthaseAldosterone synthase is a steroid hydroxylase cytochrome P450 oxidase enzyme involved in the generation of aldosterone....
(for aldosterone) or by the 11β-hydroxylase (for
corticosteroneCorticosterone 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...
). These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions). But aldosterone synthase is also able to perform a 18-oxidation. Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the
adrenal cortexSituated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.-Layers:Notably, the reticularis in...
; 11β-hydroxylase is found in the
zona fasciculataThe zona fasciculata constitutes the middle zone of the adrenal cortex, sitting directly beneath the zona glomerulosa. Constituent cells are organized into bundles or "fascicles"....
and reticularis.
Note:
aldosterone synthaseAldosterone synthase is a steroid hydroxylase cytochrome P450 oxidase enzyme involved in the generation of aldosterone....
is absent in other sections of the
adrenal glandIn 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...
.
Stimulation
Aldosterone synthesis is stimulated by several factors:
- increase in the plasma concentration of Angiotensin III, a metabolite of Angiotensin II
- increase in plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
angiotensin II, ACTH, or potassiumPotassium 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, 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 glomerulosaThe zona glomerulosa of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the adrenal gland's capsule...
, which opens the voltage-dependent calcium channelVoltage-dependent calcium channels are a group of voltage-gated ion channels found in excitable cells with a permeability to the ion Ca2+...
s.) The level of angiotensin II is regulated by angiotensin I, which is in turn regulated by the hormone reninRenin , 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...
. Potassium levels are the most sensitive stimulator of aldosterone.
- the ACTH stimulation test
The ACTH stimulation test is a medical test usually ordered and interpreted by endocrinologists to assess the functioning of the adrenal glands stress response by measuring the adrenal response to adrenocorticotropic hormone...
, which is sometimes used to stimulate the production of aldosterone along with cortisolCortisol 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,...
to determine whether primary or secondary adrenal 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...
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 an increased acidity in the blood and other body tissue . If not further qualified, it usually refers to acidity of the blood plasma....
- 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, obtained from pineal extracts. It selectively stimulates secretion of aldosterone.
The secretion of aldosterone has a
diurnalA day is a unit of time, commonly defined as an interval equal to 24 hours. It also can mean that portion of the full day during which a location is illuminated by the light of the sun...
rhythm.
Function
Aldosterone is the primary of several endogenous members of the class of
mineralocorticoidMineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
s in humans.
Deoxycorticosterone11-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...
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 , also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, is a protein that in humans is encoded by the NR3C2 gene that is located on chromosome 4q31.1-31.2.MR is a receptor with high affinity for mineralocorticoids...
s (MR) within the principal cells of the distal tubule and the collecting duct of the kidney nephron, it upregulates and activates the basolateral Na+/K+ pumpsNa+/K+-ATPase is an enzyme located in the plasma membrane in all animals.- Sodium-potassium pumps :Active transport is responsible for cells containing relatively high...
, which pumps three sodium ions out of the cell and two potassium ions into the cell. This 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 channel (ENaC
ENAC may refer to: - a French civil aeronautics academy* Epithelial sodium channel * Italian Civil Aviation Authority...
) increasing apical membrane permeability for Na+.
- Cl- is reabsorbed in conjunction with sodium cations to maintain the system's electrochemical balance.
- Aldosterone stimulates the excretion of K+ into the lumen.
- Aldosterone stimulates Na+ and water reabsorption from the gut salivary and sweat glands in exchange for K+.
- Aldosterone stimulates H+ secretion by intercalated cells in the collecting duct, regulating plasma bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
(HCO3−) levels and its acid/base balance.
- Aldosterone may act on the central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
via the posterior pituitary gland to release vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
(ADH), which serves to conserve water by direct actions on renal tubular reabsorption.
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 GFR (glomerular filtration rate).
Aldosterone, most probably acting through mineralocorticoid receptors, may positively influence neurogenesis in the dentate gyrus.
Location of receptors
SteroidA 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...
receptors are intracellular. The aldosterone mineralcorticoid receptor (MR) complex binds on the DNA to specific
hormone response elementA hormone response element is a response element for hormones, a short sequence of DNA within the promoter of a gene that is able to bind a specific hormone receptor complex and therefore regulate transcription...
, which leads to gene specific
transcriptionTranscription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
.
Some of the transcribed genes are crucial for transepithelial sodium transport, including the three
subunitsIn structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...
of the
epithelial sodium channelThe epithelial sodium channel is a membrane-bound ion-channel that is permeable for Li+-ions, protons and especially Na+-ions. It is a constitutively active ion-channel...
(ENaC), the
Na+/K+ pumpsNa+/K+-ATPase is an enzyme located in the plasma membrane in all animals.- Sodium-potassium pumps :Active transport is responsible for cells containing relatively high...
and their regulatory proteins serum and glucocorticoid-induced kinase, and
channel-inducing factorChannel-inducing factor is a regulatory protein for aldosterone receptors....
, respectively.
The mineralcorticoid receptor is stimulated by both aldosterone and cortisol, but there is a mechanism that protects the body from excess aldosterone receptor stimulation by glucocorticoids, which happen to be present at much higher concentrations than mineralcorticoids in the healthy individual. The mechanism consists of an enzyme called 11 β-hydroxysteroid dehydrogenase (11 β-HSD). This enzyme co-localizes with intracellular adrenal steroid receptors and converts cortisol (an active mineralcorticoid) into cortisone, a relatively inactive metabolite with little affinity for the MR. Licorice, which contains glycyrrhetinic acid, can inhibit 11 β-HSD and lead to a mineralcorticoid excess syndrome.
Control of aldosterone release from the adrenal cortex
The role of the renin-angiotensin systemThe renin-angiotensin system or the renin-angiotensin-aldosterone system is a hormone system that regulates blood pressure and water balance....
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.
The plasma concentration of potassiumPotassium 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...
The amount of aldosterone secreted is a direct function of the serum potassium as probably determined by sensors in the carotid artery.
ACTH
ACTH, a pituitary peptide, also has some stimulating effect on aldosterone probably by stimulating the formation of
deoxycorticosterone11-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...
, a precursor of aldosterone. Aldosterone is increased by blood loss, pregnancy, and possibly by other circumstances such as physical exertion, endotoxin shock, and burns.
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, 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 baroreceptorBaroreceptors are sensors located in the blood vessels of several mammals. They are a type of mechanoreceptor that detects the pressure of blood flowing through them, and can send messages to the central nervous system to increase or decrease total peripheral resistance and cardiac output...
s
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 role of the juxtaglomerular apparatusThe juxtaglomerular apparatus is a microscopic structure in the kidney, which regulates the function of each nephron. The juxtaglomerular apparatus is named for its proximity to the glomerulus: it is found between the vascular pole of the renal corpuscle and the returning distal convoluted tubule...
Through RAAS
The plasma concentration of sodiumSodium 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...
Aldosterone is a function of the inverse of the 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 much 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, the 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 non-morphological 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
HyperaldosteronismHyperaldosteronism, also aldosteronism, is a medical condition where too much aldosterone is produced by the adrenal glands, which can lead to lowered levels of potassium in the blood.-Types:...
is abnormally increased levels of aldosterone, while
hypoaldosteronismIn medicine , hypoaldosteronism refers to decreased levels of the hormone aldosterone.The term "isolated hypoaldosteronism" is used to describe lowered aldosterone without corresponding changes in cortisol...
is abnormally decreased levels of aldosterone.
!colspan=3| Upper limits of plasma
aldosterone
reference rangeIn health-related fields, a reference range or reference interval usually describes the variations of a measurement or value in healthy individuals...
s
|-
|rowspan=2| Upright adult, 8-10 am >
34.0 |
|
>-
| 940
|
>-
|rowspan=2| Supine adult, 8-10 am
19.0 |
|
>-
| 530
|
>-
|rowspan=2| Upright adult, 4-6 pm
23.0 |
|
>-
| 640
A measurement of aldosterone in blood may be termed a
plasma aldosterone concentration (
PAC), which may be compared to plasma renin activity (PRA) as an
aldosterone-to-renin ratioAldosterone-to-renin ratio is the mass concentration of aldosterone divided by the plasma renin activity in blood plasma. The aldosterone/renin ratio is recommended as screening tool for primary hyperaldosteronism.-Interpretation:...
.
Hyperaldosteronism
Primary aldosteronism (also known as
primary hyperaldosteronism, is characterized by the overproduction of aldosterone by the
adrenal glandIn 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...
s, when not a result of excessive renin secretion. It leads to arterial hypertension (high blood pressure) associated with hypokalemia, usually a diagnostic clue. Secondary hyperaldosteronism, on the other hand, is due to overactivity of the
renin-angiotensin systemThe renin-angiotensin system or the renin-angiotensin-aldosterone system is a hormone system that regulates blood pressure and water balance....
.
Conn'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...
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 antagonistAldosterone antagonist refers to diuretic drugs which antagonize the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure...
s.
Hypoaldosteronism
An ACTH stimulation test for aldosterone can help in determining the cause of
hypoaldosteronismIn medicine , hypoaldosteronism refers to decreased levels of the hormone aldosterone.The term "isolated hypoaldosteronism" is used to describe lowered aldosterone without corresponding changes in cortisol...
, with a low aldosterone response indicating a
primary hypoaldosteronism of the adrenals, while a large response indicating a
secondary hypoaldosteronism.