Aldosterone is a hormone that increases the reabsorption of sodium and water and the release (secretion) of potassium in the kidneys. This increases blood volume and, therefore, increases blood pressure. Many drugs, such as
spironolactoneSpironolactone is a diuretic and is used as an antiandrogen....
, lower blood pressure by blocking the aldosterone receptor. Aldosterone is part of the renin-angiotensin system.
Aldosterone is a
steroid hormoneSteroid hormones are steroids that act as hormones. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestagens...
(
mineralocorticoidMineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balance.-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:The cortex can be divided...
in the
adrenal glandIn mammals, the adrenal glands are the star-shaped endocrine glands that sit on top of the kidneys; their name indicates that position...
, and acts on the distal tubules and collecting ducts of the
kidneyThe kidneys are paired organs, which have the production of urine as their primary function. Kidneys are seen in many types of animals, including vertebrates and some invertebrates. They are part of the urinary system, but have several secondary functions concerned with homeostatic functions. ...
to cause the conservation of
sodiumSodium is a metallic element with a symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals within "group 1"...
, secretion of
potassiumPotassium is the chemical element with the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash...
, increased water retention, and increased
blood pressureBlood pressure is the pressure exerted by circulating blood on the walls of blood vessels, and is one of the principal vital signs. During each heartbeat, BP varies between a maximum and a minimum pressure...
.
Aldosterone is a hormone that increases the reabsorption of sodium and water and the release (secretion) of potassium in the kidneys. This increases blood volume and, therefore, increases blood pressure. Many drugs, such as
spironolactoneSpironolactone is a diuretic and is used as an antiandrogen....
, lower blood pressure by blocking the aldosterone receptor. Aldosterone is part of the renin-angiotensin system.
Aldosterone is a
steroid hormoneSteroid hormones are steroids that act as hormones. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestagens...
(
mineralocorticoidMineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balance.-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:The cortex can be divided...
in the
adrenal glandIn mammals, the adrenal glands are the star-shaped endocrine glands that sit on top of the kidneys; their name indicates that position...
, and acts on the distal tubules and collecting ducts of the
kidneyThe kidneys are paired organs, which have the production of urine as their primary function. Kidneys are seen in many types of animals, including vertebrates and some invertebrates. They are part of the urinary system, but have several secondary functions concerned with homeostatic functions. ...
to cause the conservation of
sodiumSodium is a metallic element with a symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals within "group 1"...
, secretion of
potassiumPotassium is the chemical element with the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash...
, increased water retention, and increased
blood pressureBlood pressure is the pressure exerted by circulating blood on the walls of blood vessels, and is one of the principal vital signs. During each heartbeat, BP varies between a maximum and a minimum pressure...
. 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 endocrine disorder in which the adrenal glands do not produce enough steroid hormones...
and increased in Conn syndrome.
It was first isolated by Simpson and Tait in 1953.
Synthesis
The corticosteroids are synthesized from
cholesterolCholesterol is a lipidic, waxy steroid found in the cell membranes and transported in the blood plasma of all animals. It is an essential component of mammalian cell membranes, where it is required to establish proper membrane permeability and fluidity...
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:The cortex can be divided...
. 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 CYP21B.-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 either mediated by the aldosterone synthase (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:The cortex can be divided...
; 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.It converts 11-deoxycorticosterone to corticosterone, to 18-hydroxycorticosterone, and finally to aldosterone:...
is absent in other sections of the
adrenal glandIn mammals, the adrenal glands are the star-shaped endocrine glands that sit on top of the kidneys; their name indicates that position...
.
Stimulation
Aldosterone synthesis is stimulated by several factors:
- by increase in the plasma concentration of Angiotensin III, a metabolite of Angiotensin II.
- by increased plasma
Blood plasma is the yellow liquid component of blood, in which the blood cells in whole blood would normally be suspended. It makes up about 55% of the total blood volume. It is mostly water and contains dissolved proteins, glucose, clotting factors, mineral ions, hormones and carbon dioxide...
angiotensin II, ACTH, or potassiumPotassium is the chemical element with the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash...
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+. At physiologic or resting membrane potential, VDCCs are normally closed...
s.) The level of angiotensin II is regulated by angiotensin I, which is in turn regulated by the hormone reninRenin , also known as Angiotensinogenase, is a circumsized enzyme that participates in the body's renin-angiotensin system 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...
is sometimes used to stimulate the production of aldosterone along with cortisolCortisol is a corticosteroid hormone or glucocorticoid produced by the adrenal cortex, that is part of the adrenal gland . It is usually referred to as the "stress hormone" as it is involved in response to stress and anxiety, controlled by CRH...
to determine if 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.
- ACTH has only a minor role in regulating aldosterone production; with hypopituitarism there is no atrophy of the zona glomerulosa.
- by plasma acidosis
Acidosis is an increased acidity . If not further qualified, it usually refers to acidity of the blood plasma....
.
- by 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.
- by 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 equivalent to approximately 24 hours. It is not an SI unit but it is accepted for use with SI. The SI unit of time is the second....
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 balance.-Physiology:...
s in human.
Deoxycorticosterone11-Deoxycorticosterone is a steroid hormone produced by the adrenal gland that possess 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. It has no...
is another important member of this class. At the late distal tubule & collecting duct, aldosterone has three main actions:
- Acting on the nuclear mineralocorticoid receptor
The mineralocorticoid receptor , also called aldosterone receptor, is officially labelled nuclear receptor subfamily 3, group C, member 2, and 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 increases the permeability of the apical (luminal) membrane to potassium and sodium 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 the well-established observation that cells...
, stimulating ATPAdenosine-5'-triphosphate is a multifunctional nucleotide that plays an important role in cell biology as a coenzyme, that is, the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
hydrolysis leading to phosphorylation of the pump and a conformational change in the pump exposes the Na+ ions to the outside. The phosphorylated form of the pump has a low affinity for Na+ ions, hence reabsorbing sodium (Na+) ions and water into the blood, and secreting potassium (K+) ions into the urine. (Chlorine anions are also reabsorbed in conjunction with sodium cations to maintain the system's electrochemical balance.)
- 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 functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
via the posterior pituitary gland to release vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a hormone found in most mammals, including humans. Vasopressin is a peptide hormone. It is derived from a preprohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the...
(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
Unlike neuroreceptors, classic
steroidA steroid is a terpenoid lipid characterized by its sterane core and additional functional groups. The core is a carbon structure of four fused rings: three cyclohexane rings and one cyclopentane ring. The steroids vary by the functional groups attached to these rings and the oxidation state of the...
receptors are intracellularly located. The aldosterone/MR receptor 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, or RNA synthesis, is the process of creating an equivalent 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 in the presence of the correct enzymes...
.
Some of the transcribed genes are crucial for transepithelial sodium transport, including the three
subunitIn 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...
s 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...
, 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 the well-established observation that cells...
and their regulatory proteins serum and glucocorticoid-induced kinase, and
channel-inducing factorChannel-inducing factor is a regulatory protein for aldosterone receptors....
respectively.
Control of aldosterone release from the Adrenal Cortex
- The role of the renin-angiotensin system
The 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 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 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 baroreceptor
Baroreceptors are sensors located in the blood vessels of the human body. They detect 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 in the carotid artery decreases aldosterone
- The role of the juxtaglomerular apparatus
The 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...
:
- The plasma concentration of potassium
Potassium is the chemical element with the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash...
:
The amount of aldosterone secreted is a direct function of the serum potassium as probably determined by sensors in the carotid artery.
- The plasma concentration of sodium
Sodium is a metallic element with a symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals within "group 1"...
:
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.
- Miscellaneous regulation:
ACTH, a pituitary peptide, also has some stimulating effect on aldosterone probably by stimulating
deoxycorticosterone11-Deoxycorticosterone is a steroid hormone produced by the adrenal gland that possess 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. It has no...
formation which is a precursor of aldosterone. Aldosterone is increased by blood loss, pregnancy, and possibly by other circumstances such as physical exertion, endotoxin shock, and burns.
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.