Mineralocorticoids are a class of steroid hormone

Steroid hormone

A 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...

s characterised by their similarity to 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 their influence on salt and water balances.

Physiology

The name mineralocorticoid derives from early observations that these hormones were involved in the retention of 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...

, a mineral

Mineral

A mineral is a naturally occurring solid chemical substance formed through biogeochemical processes, having characteristic chemical composition, highly ordered atomic structure, and specific physical properties. By comparison, a rock is an aggregate of minerals and/or mineraloids and does not...

. The primary endogenous

Endogenous

Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...

 mineralocorticoid 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...

, although a number of other endogenous hormones (including progesterone

Progesterone

Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...

 and deoxycorticosterone

Deoxycorticosterone

11-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...

) have mineralocorticoid function.

Aldosterone acts on the kidneys to provide active reabsorption of 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...

 and an associated passive reabsorption of water

Water

Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...

, as well as the active secretion of 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...

 in the principal cells of the cortical collecting tubule and active secretion of proton

Proton

The proton is a subatomic particle with the symbol or and a positive electric charge of 1 elementary charge. One or more protons are present in the nucleus of each atom, along with neutrons. The number of protons in each atom is its atomic number....

s via proton ATPase

ATPase

ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...

s in the lumenal membrane of the intercalated cells of the collecting tubule. This in turn results in an increase of blood pressure

Blood pressure

Blood 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...

 and blood volume

Blood volume

Blood volume is the volume of blood in the circulatory system of an individual.-Humans:A typical adult has a blood volume of approximately between 4.7 and 5 liters, with females generally having less blood volume than males....

.

Aldosterone is produced in the cortex of the adrenal gland

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...

 and its secretion is mediated principally by angiotensin II but also by adrenocorticotrophic hormone (ACTH) and local 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.

Mode of action

The effects of mineralocorticoids are mediated by slow genomic mechanisms through nuclear receptor

Nuclear receptor

In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...

s as well as by fast nongenomic mechanisms through membrane-associated receptors and signaling cascades.

Genomic mechanisms

Mineralocorticoids bind to the cytosolic mineralocorticoid receptor

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...

. This type of receptor

Receptor (biochemistry)

In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

 gets activated upon ligand

Ligand

In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...

 binding. After a hormone binds to the corresponding receptor, the newly formed receptor-ligand complex translocates itself into the cell nucleus

Cell nucleus

In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

, where it binds to many hormone response elements (HRE

Hormone response element

A 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...

) in the promoter region of the target gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s in the DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

.

The opposite mechanism is called transrepression

Transrepression

In the field of molecular biology, transrepression is a process whereby one protein represses the activity of a second protein through a protein-protein interaction...

. The hormone receptor

Hormone receptor

A hormone receptor is a receptor protein on the surface of a cell or in its interior that binds to a specific hormone. The hormone causes many changes to take place in the cell....

 without ligand binding interacts with heat shock protein

Heat shock protein

Heat shock proteins are a class of functionally related proteins involved in the folding and unfolding of other proteins. Their expression is increased when cells are exposed to elevated temperatures or other stress. This increase in expression is transcriptionally regulated...

s and prevents the transcription

Transcription (genetics)

Transcription 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...

 of targeted genes.

Aldosterone 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,...

 (a glucosteroid) have similar affinity for the mineralocorticoid receptor; however, glucocorticoids circulate at roughly 100 times the level of mineralocorticoids. An enzyme exists in mineralocorticoid target tissues to prevent overstimulation by glucocorticoids. This enzyme, 11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2

Protein:HSD11B2

Corticosteroid 11-β-dehydrogenase isozyme 2 also known as 11-β-hydroxysteroid dehydrogenase 2 is an enzyme that in humans is encoded by the HSD11B2 gene.- Function :...

), catalyzes the deactivation of glucocorticoids to 11-dehydro metabolites. Licorice is known to be an inhibitor of this enzyme and chronic consumption can result in a condition known as pseudohyperaldosteronism

Pseudohyperaldosteronism

Pseudohyperaldosteronism is a medical condition that mimics hyperaldosteronism. Like hyperaldosteronism, it produces hypertension associated with low plasma renin activity, and metabolic alkalosis associated with hypokalemia...

.

18 hydroxy 11 deoxycorticosterone

18 hydroxy 11 deoxycorticosterone (also designated 18OH-DOC) is a steroid hormone probably used to conserve 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...

 and stimulate hydrogen ion

Hydrogen ion

Hydrogen ion is recommended by IUPAC as a general term for all ions of hydrogen and its isotopes.Depending on the charge of the ion, two different classes can be distinguished: positively charged ions and negatively charged ions....

 (or acid) excretion. 18OH-DOC lowers urine pH but has no effect on 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...

 excretion. This would seem to indicate that 18OH-DOC's primary purpose is to stimulate hydrogen ion or ammonium

Ammonium

The ammonium cation is a positively charged polyatomic cation with the chemical formula NH. It is formed by the protonation of ammonia...

 excretion. Under low sodium intake 18 OH DOC is increased in serum. There is a marked increase in serum 18OH DOC after injection of insulin and this may be due to the hypokalemic (low serum potassium) tendency after a rise in insulin which in turn would make the serum more acidic. Since 18OH-DOC lowers urine pH (increases acidity) but has no effect on potassium excretion, this would seem to indicate that 18OH-DOC's primary purpose is to stimulate hydrogen ion or ammonium excretion. Its use by the body to conserve potassium would be indirect by virtue of hydrogen ion's interference with potassium excretion. This interference is further indicated because injecting sodium bicarbonate or even hyperventilating (breathing rapidly beyond need) can triple potassium excretion. The daily rhythm for potassium and hydrogen ion excretion show a rather close inverse relationship, which gives additional circumstantial support to the supposition that they compete at a common site. 18OH-DOC is strongly dependent on the potassium cell or plasma content, because in potassium-deficient rats markedly less 18OH-DOC is converted to 18OH-corticosterone and less yet if sodium is deficient.

ACTH (a peptide hormone) has a large effect on 18OH DOC, causing 18OH DOC to go down to zero when ACTH does. This could be for the primary purpose of keeping serum immune enzymes and cell fluids at a high pH

PH

In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...

 (alkaline) during internal infection, but not doing so during the intestinal infection of diarrhea, during which disease the resulting dehydration forces ACTH to decline. It probably is important normally to keep the vacuoles where pathogens are digested at a high pH because if the pH or alkalinity is not high enough, the pathogens inside the immune cells are not digested and thus released intact. So when an intestinal disease is not calling for ACTH to decline, the indirect potassium conserving attribute of 18OH-DOC by virtue of stimulating acid excretion would be valuable, as would increased acid excretion during internal disease.

18OH DOC may act primarily by blocking aldosterone's effect on potassium, and must have aldosterone to assist it with sodium. Nichols, et al., have been able to show that injection of 18OH-DOC, which raised blood levels of this hormone ten times, were more retentive of sodium than a similar amount of aldosterone. So there must be a synergism involved. At the same time, the ratio of sodium to potassium excretion declined very little for 18OH-DOC, while for aldosterone, the ratio fell to as little as 1/3 that of control men. This implies a considerable sparing of potassium by 18OH-DOC. Urine potassium excretion is not altered by 18OH-DOC injection.

Angiotensin II has very little effect on 18OH-DOC and is ambiguous (nor does serum potassium above 4.8 mEq/liter (187 mg)). This last is not surprising since 18OH-DOC should not be used by the body at high serum potassium. Under low sodium intake, 18OH-DOC rises in the serum. ACTH causes a marked increase in 18OH-DOC, probably by a generalized affect on the 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"....

 of the adrenal cortex

Adrenal cortex

Situated 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...

 where 18OH-DOC is synthesized. So when it is necessary for sodium to be unloaded during the dehydration induced decline of ACTH during diarrhea in order to preserve osmotic pressure, the resulting 18OH-DOC decline would assist in this.

18OH-DOC is deeply involved in one of the three forms (at least) of hypertension

Hypertension

Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

 (high blood pressure).

Pathophysiology

Hyperaldosteronism

Hyperaldosteronism

Hyperaldosteronism, 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:...

 (the syndrome caused by elevated aldosterone) generally results from adrenal cancers. The two main resulting problems:

1. Hypertension
   Hypertension
   Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
   
    and edema
   Edema
   Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
   
    due to excessive Na+ and water retention.
2. Accelerated excretion of potassium ions
   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...
   
    (K+). With extreme K+ loss there is muscle weakness and eventually paralysis.

Underproduction, or hypoaldosteronism, leads to the salt-wasting state associated with Addison's disease

Addison's disease

Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...

, although classical congenital adrenal hyperplasia

Congenital adrenal hyperplasia

Congenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....

 and other disease states may also cause this situation.

Pharmacology

An example of a synthetic mineralocorticoid is fludrocortisone

Fludrocortisone

Fludrocortisone is a synthetic corticosteroid with moderate glucocorticoid potency and much greater mineralocorticoid potency. The brand name in the U.S. and Canada is Florinef.-Uses:...

 (Florinef). Important mineralocorticoid inhibitors are spironolactone

Spironolactone

Spironolactone , 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...

 and eplerenone

Eplerenone

Eplerenone is an aldosterone antagonist used as an adjunct in the management of chronic heart failure. It is similar to the diuretic spironolactone, though it may be more specific for the mineralocorticoid receptor and is specifically marketed for reducing cardiovascular risk in patients...

.