11-Deoxycorticosterone
Encyclopedia
11-Deoxycorticosterone (or deoxycorticosterone or 21-hydroxyprogesterone) 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
. It has no significant glucocorticoid
activity.
by 21β-hydroxylase and is converted to corticosterone
by 11β-hydroxylase
. Corticosterone is then converted to aldosterone by aldosterone synthase
.
Most of the deoxycorticosterone (also called cortexone, 11 desoxycorticosterone, deoxycortone, desoxycortone, compound B, DOC) is secreted by the zona fasiculata of the adrenal cortex which also secretes cortisol, and a small amount by the zona glomerulosa
, which secretes aldosterone. DOC stimulates the collecting tubules (the tubules which branch together to feed the bladder) to continue to excrete potassium in much the same way that aldosterone
does but not like aldosterone in the end of the looped tubules (distal). At the same time it is not nearly so rigorous at retaining sodium as aldosterone, more than 20 times less. DOC accounts for only 1% of the sodium retention normally In addition to its inherent lack of vigor there is an escape mechanism controlled by an unknown non steroid hormone which overrides DOC's sodium conserving power after a few days just as aldosterone is overridden also. This hormone may be the peptide hormone kallikrein
, which is augmented by DOC and suppressed by aldosterone. If sodium becomes very high, DOC also increases urine flow. DOC has about 1/20 of the sodium retaining power of aldosterone and is said to be as little as one per cent of aldosterone at high water intakes. Since DOC has about 1/5 the potassium excreting power of aldosterone it probably must have aldosterone's help if the serum potassium content becomes too high. DOC's injections do not cause much additional potassium excretion when sodium intake is low. This is probably because aldosterone is already stimulating potassium outflow. When sodium is low DOC probably would not have to be present, but when sodium rises aldosterone declines considerably, and DOC probably tends to take over.
DOC has a similar feedback with respect to potassium as aldosterone. A rise in serum potassium causes a rise in DOC secretion. However, sodium has little effect, and what effect it does have is direct. Angiotensin
(the blood pressure hormone) has little effect on DOC, but DOC causes a rapid fall in renin
, and therefore angiotensin I, the precursor of angiotensin II. Therefore, DOC must be indirectly inhibiting aldosterone since aldosterone depends on angiotensin II. Sodium, and therefore blood volume, is difficult to regulate internally. That is, when a large dose of sodium threatens the body with high blood pressure, it cannot be resolved by transferring sodium to the intracellular
(inside the cell) space. The red cells would have been possible, but that would not change the blood volume. Potassium, on the other hand, can be moved into the large intracellular space, and apparently it is by DOC in rabbits. Thus, a problem in high blood potassium can be resolved somewhat without jettisoning too much of what is sometimes a dangerously scarce mineral that can not be pumped actively independently from sodium. It is imperative to keep total potassium adequate because a deficiency causes the heart to lose force. Movement of potassium into the cells would intensify the sodium problem somewhat because when potassium moves into the cell, a somewhat smaller amount of sodium moves out. Thus, it is desirable to resolve the blood pressure problem as much as possible by the fall in renin
above, therefore avoiding loss of sodium, which was usually in very short supply on the African savannas where human ancestors probably evolved.
The resemblance of the pattern of the electromotive forces produced by DOC in the kidney tubules to normal potassium intake, and the total dissimilarity of their shape as produced by potassium deficient tubules, would tend to support the above view. The above attributes are consistent with a hormone which is relied upon to unload both excess sodium and potassium. DOC's action in augmenting kallikrein, the peptide hormone thought to be the sodium "escape hormone," and aldosterone's action in suppressing it, is also supportive of the above concept.
ACTH has more effect on DOC than it does on aldosterone. This may be to give the immune system control over the electrolyte regulation during diarrhea since during dehydration
, aldosterone virtually disappears any way even though renin and angiotensin rise high. It is for this aldosterone disappearance reason that potassium supplements are very dangerous during dehydration and must not be attempted until at least one hour after rehydration in order to give time for the hormones to reach the nucleus.
DOC's primary purpose is to regulate electrolytes. However, it has other effects, such as to remove potassium from leucocytes and muscle, depress glycogen formation and to stimulate copper containing lysyl oxidase enzyme and connective tissue, which attributes may be used by the body to help survive during potassium wasting intestinal diseases
The greater efficiency of DOC in permitting sodium excretion (or perhaps it should be expressed as inefficiency at retention) must be partly through morphological changes in the kidney cells because escape from DOC’s sodium retention takes several days to materialize, and when it does, these cells are much more efficient at unloading sodium if sodium is then added than cells accustomed to a prior low intake. Thus, paradoxically, a low salt intake should be protective against loss of sodium in perspiration.
Progesterone
prevents some of the loss of potassium by DOC.
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...
produced by 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...
that possesses mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
activity and acts as a precursor
Precursor (chemistry)
In chemistry, a precursor is a compound that participates in the chemical reaction that produces another compound. In biochemistry, the term "precursor" is used more specifically to refer to a chemical compound preceding another in a metabolic pathway....
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...
. As its names indicate, it can be understood as 21-hydroxy
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
- variant of 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...
or a 11-deoxy- variant of corticosterone
Corticosterone
Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...
. It has no significant glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
activity.
Deoxycorticosterone physiology
11-Deoxycorticosterone is a precursor molecule for the production of aldosterone. The major pathway for aldosterone production is in the adrenal glomerulosa zone of the adrenal gland. It is not a major secretory hormone. It is produced from progesteroneProgesterone
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...
by 21β-hydroxylase and is converted to corticosterone
Corticosterone
Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...
by 11β-hydroxylase
Steroid 11-beta-hydroxylase
Steroid 11β-hydroxylase is a steroid hydroxylase found in the zona fasciculata. Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the CYP11B1 gene....
. Corticosterone is then converted to aldosterone by aldosterone synthase
Aldosterone synthase
Aldosterone synthase is a steroid hydroxylase cytochrome P450 oxidase enzyme involved in the generation of aldosterone....
.
Most of the deoxycorticosterone (also called cortexone, 11 desoxycorticosterone, deoxycortone, desoxycortone, compound B, DOC) is secreted by the zona fasiculata of the adrenal cortex which also secretes cortisol, and a small amount by the zona glomerulosa
Zona glomerulosa
The zona glomerulosa of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the adrenal gland's capsule...
, which secretes aldosterone. DOC stimulates the collecting tubules (the tubules which branch together to feed the bladder) to continue to excrete potassium in much the same way that 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...
does but not like aldosterone in the end of the looped tubules (distal). At the same time it is not nearly so rigorous at retaining sodium as aldosterone, more than 20 times less. DOC accounts for only 1% of the sodium retention normally In addition to its inherent lack of vigor there is an escape mechanism controlled by an unknown non steroid hormone which overrides DOC's sodium conserving power after a few days just as aldosterone is overridden also. This hormone may be the peptide hormone kallikrein
Kallikrein
Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein has no known homologue, while tissue kallikrein-related peptidases encode a family of fifteen closely related serine proteases...
, which is augmented by DOC and suppressed by aldosterone. If sodium becomes very high, DOC also increases urine flow. DOC has about 1/20 of the sodium retaining power of aldosterone and is said to be as little as one per cent of aldosterone at high water intakes. Since DOC has about 1/5 the potassium excreting power of aldosterone it probably must have aldosterone's help if the serum potassium content becomes too high. DOC's injections do not cause much additional potassium excretion when sodium intake is low. This is probably because aldosterone is already stimulating potassium outflow. When sodium is low DOC probably would not have to be present, but when sodium rises aldosterone declines considerably, and DOC probably tends to take over.
DOC has a similar feedback with respect to potassium as aldosterone. A rise in serum potassium causes a rise in DOC secretion. However, sodium has little effect, and what effect it does have is direct. Angiotensin
Angiotensin
Angiotensin, a peptide hormone, causes blood vessels to constrict, and drives blood pressure up. It is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. Angiotensin also stimulates the release of aldosterone, another hormone, from the adrenal cortex...
(the blood pressure hormone) has little effect on DOC, but DOC causes a rapid fall in renin
Renin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
, and therefore angiotensin I, the precursor of angiotensin II. Therefore, DOC must be indirectly inhibiting aldosterone since aldosterone depends on angiotensin II. Sodium, and therefore blood volume, is difficult to regulate internally. That is, when a large dose of sodium threatens the body with high blood pressure, it cannot be resolved by transferring sodium to the intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
(inside the cell) space. The red cells would have been possible, but that would not change the blood volume. Potassium, on the other hand, can be moved into the large intracellular space, and apparently it is by DOC in rabbits. Thus, a problem in high blood potassium can be resolved somewhat without jettisoning too much of what is sometimes a dangerously scarce mineral that can not be pumped actively independently from sodium. It is imperative to keep total potassium adequate because a deficiency causes the heart to lose force. Movement of potassium into the cells would intensify the sodium problem somewhat because when potassium moves into the cell, a somewhat smaller amount of sodium moves out. Thus, it is desirable to resolve the blood pressure problem as much as possible by the fall in renin
Renin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
above, therefore avoiding loss of sodium, which was usually in very short supply on the African savannas where human ancestors probably evolved.
The resemblance of the pattern of the electromotive forces produced by DOC in the kidney tubules to normal potassium intake, and the total dissimilarity of their shape as produced by potassium deficient tubules, would tend to support the above view. The above attributes are consistent with a hormone which is relied upon to unload both excess sodium and potassium. DOC's action in augmenting kallikrein, the peptide hormone thought to be the sodium "escape hormone," and aldosterone's action in suppressing it, is also supportive of the above concept.
ACTH has more effect on DOC than it does on aldosterone. This may be to give the immune system control over the electrolyte regulation during diarrhea since during dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
, aldosterone virtually disappears any way even though renin and angiotensin rise high. It is for this aldosterone disappearance reason that potassium supplements are very dangerous during dehydration and must not be attempted until at least one hour after rehydration in order to give time for the hormones to reach the nucleus.
DOC's primary purpose is to regulate electrolytes. However, it has other effects, such as to remove potassium from leucocytes and muscle, depress glycogen formation and to stimulate copper containing lysyl oxidase enzyme and connective tissue, which attributes may be used by the body to help survive during potassium wasting intestinal diseases
The greater efficiency of DOC in permitting sodium excretion (or perhaps it should be expressed as inefficiency at retention) must be partly through morphological changes in the kidney cells because escape from DOC’s sodium retention takes several days to materialize, and when it does, these cells are much more efficient at unloading sodium if sodium is then added than cells accustomed to a prior low intake. Thus, paradoxically, a low salt intake should be protective against loss of sodium in perspiration.
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...
prevents some of the loss of potassium by DOC.