11-Deoxycorticosterone

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Contents

11-Deoxycorticosterone
11-Deoxycorticosterone.svg
Names
IUPAC name
21-Hydroxypregn-4-ene-3,20-dione
Systematic IUPAC name
(1S,3aS,3bS,9aR,9bS,11aS)-1-(Hydroxyacetyl)-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-7H-cyclopenta[a]phenanthren-7-one
Other names
Deoxycorticosterone; Desoxycortone; Deoxycortone; Cortexone; 21-Hydroxyprogesterone; 21-Hydroxy-4-pregnene-3,20-dione; Reichstein's substance Q; Kendall's desoxy compound B; NSC-11319
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.543 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C21H30O3/c1-20-9-7-14(23)11-13(20)3-4-15-16-5-6-18(19(24)12-22)21(16,2)10-8-17(15)20/h11,15-18,22H,3-10,12H2,1-2H3/t15-,16-,17-,18+,20-,21-/m0/s1
    Key: ZESRJSPZRDMNHY-YFWFAHHUSA-N
  • O=C4\C=C2/[C@]([C@H]1CC[C@@]3([C@@H](C(=O)CO)CC[C@H]3[C@@H]1CC2)C)(C)CC4
Properties
C21H30O3
Molar mass 330.461 g/mol
Pharmacology
H02AA03 ( WHO )
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

11-Deoxycorticosterone (DOC), or simply deoxycorticosterone, also known as 21-hydroxyprogesterone, as well as desoxycortone (INN), deoxycortone, and cortexone, [1] [2] is a steroid hormone produced by the adrenal gland that possesses mineralocorticoid activity and acts as a precursor to aldosterone. [3] It is an active (Na+-retaining) mineralocorticoid. [4] As its names indicate, 11-deoxycorticosterone can be understood as the 21-hydroxy-variant of progesterone or as the 11-deoxy-variant of corticosterone.

DOCA is the abbreviation for the ester 11-deoxycorticosterone acetate. [5]

Biological activity

DOC is a potent mineralocorticoid but is virtually devoid of glucocorticoid activity. [6] [7] [8] However, 11β-hydroxylation of DOC produces corticosterone and confers glucocorticoid activity, along with 10-fold reduced mineralocorticoid activity. [8] In addition to its mineralocorticoid activity, DOC has been found to possess one-third to one-tenth the potency of progesterone as a progestogen when administered systematically to rabbits. [9] However, it has no such activity when applied directly to the uterine mucosa of mice. [9] The discrepancy may be related to the fact that DOC can be converted into progesterone in vivo . [9]

Biological role

DOC 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 progesterone by 21β-hydroxylase and is converted to corticosterone by 11β-hydroxylase. Corticosterone is then converted to aldosterone by aldosterone synthase. [10]

Most of the DOC is secreted by the zona fasciculata 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) [11] 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). [12] At the same time it is not nearly so rigorous at retaining sodium as aldosterone, [13] more than 20 times less. DOC accounts for only 1% of the sodium retention normally [14] In addition to its inherent lack of vigor there is an escape mechanism controlled by an unknown non steroid hormone [15] which overrides DOC's sodium conserving power after a few days just as aldosterone is overridden also. [16] This hormone may be the peptide hormone kallikrein, [17] which is augmented by DOC and suppressed by aldosterone. [18] If sodium becomes very high, DOC also increases urine flow. [11] DOC has about 1/20 of the sodium retaining power of aldosterone, [19] and is said to be as little as one per cent of aldosterone at high water intakes. [20] Since DOC has about 1/5 the potassium excreting power of aldosterone, [19] 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. [21] 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.[ citation needed ]

DOC has a similar feedback with respect to potassium as aldosterone. A rise in serum potassium causes a rise in DOC secretion. [22] However, sodium has little effect, [23] and what effect it does have is direct. [19] Angiotensin (the blood pressure hormone) has little effect on DOC, [22] but DOC causes a rapid fall in renin, and therefore angiotensin I, the precursor of angiotensin II. [24] 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. [24] 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. [25] 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. [26] 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.[ citation needed ]

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, [11] 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, [18] 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 [27] even though renin and angiotensin rise high. It is because aldosterone disappears that potassium supplements are very dangerous during dehydration and must not be attempted until at least one hour after rehydration so the hormones can reach the nucleus.

DOC's primary purpose is to regulate electrolytes. However, it has other effects, such as to remove potassium from leucocytes [28] and muscle, [29] depress glycogen formation [30] and to stimulate copper containing lysyl oxidase enzyme and connective tissue, [31] 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. [32]

Additional images

See also

Related Research Articles

<span class="mw-page-title-main">Adrenal gland</span> Endocrine gland

The adrenal 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 which produces steroid hormones and an inner medulla. The adrenal cortex itself is divided into three main zones: the zona glomerulosa, the zona fasciculata and the zona reticularis.

<span class="mw-page-title-main">Renin</span> Aspartic protease protein and enzyme

Renin, 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 renin-angiotensin-aldosterone axis—that increases the volume of extracellular fluid and causes arterial vasoconstriction. Thus, it increases the body's mean arterial blood pressure.

<span class="mw-page-title-main">Renin–angiotensin system</span> Hormone 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.

<span class="mw-page-title-main">Angiotensin</span> Group of peptide hormones in mammals

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 adrenal cortex to promote sodium retention by the kidneys.

<span class="mw-page-title-main">Adrenal cortex</span> Cortex of the adrenal gland

The adrenal cortex is the outer region and also the largest part of the adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is also a secondary site of androgen synthesis.

<span class="mw-page-title-main">Aldosterone</span> Mineralocorticoid steroid hormone

Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a central role in the homeostatic regulation of blood pressure, plasma sodium (Na+), and potassium (K+) levels. It does so primarily by acting on the mineralocorticoid receptors in the distal tubules and collecting ducts of the nephron. It influences the reabsorption of sodium and excretion of potassium (from and into the tubular fluids, respectively) of the kidney, thereby indirectly influencing water retention or loss, blood pressure, and blood volume. When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and kidney disease. Aldosterone has exactly the opposite function of the atrial natriuretic hormone secreted by the heart.

<span class="mw-page-title-main">Renal physiology</span> Study of the physiology of the kidney

Renal physiology is the study of the physiology of the kidney. This encompasses all functions of the kidney, including maintenance of acid-base balance; regulation of fluid balance; regulation of sodium, potassium, and other electrolytes; clearance of toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D.

<span class="mw-page-title-main">Mineralocorticoid</span> Group of corticosteroids

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. The primary mineralocorticoid is aldosterone.

<span class="mw-page-title-main">Adrenal insufficiency</span> Insufficient production of steroid hormones by the adrenal glands

Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands—also referred to as the adrenal cortex—normally secrete glucocorticoids, mineralocorticoids, and androgens. These hormones are important in regulating blood pressure, electrolytes, and metabolism as a whole. Deficiency of these hormones leads to symptoms ranging from abdominal pain, vomiting, muscle weakness and fatigue, low blood pressure, depression, mood and personality changes to organ failure and shock. Adrenal crisis may occur if a person having adrenal insufficiency experiences stresses, such as an accident, injury, surgery, or severe infection; this is a life-threatening medical condition resulting from severe deficiency of cortisol in the body. Death may quickly follow.

<span class="mw-page-title-main">Hyperkalemia</span> Excess potassium in the blood

Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5 mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasionally when severe it can cause palpitations, muscle pain, muscle weakness, or numbness. Hyperkalemia can cause an abnormal heart rhythm which can result in cardiac arrest and death.

<span class="mw-page-title-main">Potassium-sparing diuretic</span> Drugs that cause diuresis without causing potassium loss in the urine and leading to hyperkalemia

Potassium-sparing diuretics or antikaliuretics refer 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 aldosterone antagonists can also be used for treatment of primary hyperaldosteronism. Spironolactone, a steroidal aldosterone antagonist, is also used in management of female hirsutism and acne from PCOS or other causes.

<span class="mw-page-title-main">Hypoaldosteronism</span> Medical condition

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.

<span class="mw-page-title-main">Zona glomerulosa</span> Part of the adrenal gland

The zona glomerulosa 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.

<span class="mw-page-title-main">Hyperaldosteronism</span> Excess aldosterone in the body

Hyperaldosteronism is a medical condition wherein too much aldosterone is produced. High aldosterone levels can lead to lowered levels of potassium in the blood (hypokalemia) and increased hydrogen ion excretion (alkalosis). Aldosterone is normally produced in the adrenal glands.

<span class="mw-page-title-main">Mineralocorticoid receptor antagonist</span> Drug class

A mineralocorticoid receptor antagonist or aldosterone antagonist, is a diuretic drug which antagonizes 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. Spironolactone, the first member of the class, is also used in the management of hyperaldosteronism and female hirsutism. Most antimineralocorticoids, including spironolactone, are steroidal spirolactones. Finerenone is a nonsteroidal antimineralocorticoid.

<span class="mw-page-title-main">Bartter syndrome</span> Medical condition

Bartter syndrome (BS) is a rare inherited disease characterised by a defect in the thick ascending limb of the loop of Henle, which results in low potassium levels (hypokalemia), increased blood pH (alkalosis), and normal to low blood pressure. There are two types of Bartter syndrome: neonatal and classic. A closely associated disorder, Gitelman syndrome, is milder than both subtypes of Bartter syndrome.

Pseudohyperaldosteronism is a medical condition which mimics the effects of elevated aldosterone (hyperaldosteronism) by presenting with high blood pressure, low blood potassium levels (hypokalemia), metabolic alkalosis, and low levels of plasma renin activity (PRA). However, unlike hyperaldosteronism, this conditions exhibits low or normal levels of aldosterone in the blood. Causes include genetic disorders, acquired conditions, metabolic disorders, and dietary imbalances including excessive consumption of licorice. Confirmatory diagnosis depends on the specific cause and may involve blood tests, urine tests, or genetic testing; however, all forms of this condition exhibit abnormally low concentrations of both plasma renin activity (PRA) and plasma aldosterone concentration (PAC) which differentiates this group of conditions from other forms of secondary hypertension. Treatment is tailored to the specific cause and focuses on symptom control, blood pressure management, and avoidance of triggers.

<span class="mw-page-title-main">Aldosterone synthase</span> Protein-coding gene in the species Homo sapiens

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 catalyzes sequential hydroxylations of the steroid angular methyl group at C18 after initial 11β-hydroxylation. It is encoded by the CYP11B2 gene in humans.

<span class="mw-page-title-main">11-Deoxycortisol</span> Chemical compound

11-Deoxycortisol, also known as cortodoxone (INN), cortexolone as well as 17α,21-dihydroxyprogesterone or 17α,21-dihydroxypregn-4-ene-3,20-dione, is an endogenous glucocorticoid steroid hormone, and a metabolic intermediate toward cortisol. It was first described by Tadeusz Reichstein in 1938 as Substance S, thus has also been referred to as Reichstein's Substance S or Compound S.

Glucocorticoid remediable aldosteronism also describable as aldosterone synthase hyperactivity, is an autosomal dominant disorder in which the increase in aldosterone secretion produced by ACTH is no longer transient.

References

  1. ↑ Buckingham, MacDonald & Heilbron 1995.
  2. ↑ Swiss Pharmaceutical Society 2011.
  3. ↑ Costanzo 2014.
  4. ↑ Harper's Illustrated Biochemistry 30th Edition
  5. ↑ Wang D, Luo Y, Myakala K, Orlicky DJ, Dobrinskikh E, Wang X, Levi M (August 2017). "Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats". Scientific Reports. 7 (1): 9793. Bibcode:2017NatSR...7.9793W. doi:10.1038/s41598-017-09470-0. PMC   5574886 . PMID   28851937.
  6. ↑ Lan NC, Graham B, Bartter FC, Baxter JD (February 1982). "Binding of steroids to mineralocorticoid receptors: implications for in vivo occupancy by glucocorticoids". J Clin Endocrinol Metab. 54 (2): 332–42. doi:10.1210/jcem-54-2-332. PMID   6274900.
  7. ↑ Funder JW (January 2005). "Mineralocorticoid receptors: distribution and activation". Heart Fail Rev. 10 (1): 15–22. doi:10.1007/s10741-005-2344-2. PMID   15947887. S2CID   1423344.
  8. 1 2 Goodman HM (28 July 2010). Basic Medical Endocrinology. Academic Press. p. 64. ISBN   978-0-08-092055-9.
  9. 1 2 3 The Adrenocortical Hormones: Their Origin · Chemistry, Physiology, and Pharmacology. Springer Science & Business Media. 27 November 2013. p. 610. ISBN   978-3-642-88385-9.
  10. ↑ Lieberman, Marks & Peet 2012.
  11. 1 2 3 O'Neil & Helman 1977.
  12. ↑ Peterson & Wright 1977.
  13. ↑ Ellinghaus 1971.
  14. ↑ Ruch & Fulton 1960.
  15. ↑ Pearce et al. 1969.
  16. ↑ Schacht, Lowenstein & Baldwin 1971.
  17. ↑ Majima et al. 1999.
  18. 1 2 Bönner et al. 1981.
  19. 1 2 3 Oddie, Coghlan & Scoggins 1972.
  20. ↑ Desaulles 1958.
  21. ↑ Bauer & Gauntner 1979.
  22. 1 2 Brown, Strott & Liddle 1972.
  23. ↑ Schambelan & Biglieri 1972.
  24. 1 2 Grekin, Terris & Bohr 1980.
  25. ↑ Abbrecht 1972.
  26. ↑ Rubini & Chojnacki 1972.
  27. ↑ Merrill, Skelton & Cowley 1986.
  28. ↑ Wilson 1957.
  29. ↑ Tobian & Binion 1954.
  30. ↑ Bartlett & MacKay 1949.
  31. ↑ Pospísilová & Pospísil 1970.
  32. ↑ Wambach & Higgins 1979.

Sources

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