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11-Deoxycorticosterone

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11-Deoxycorticosterone
Clinical data
ATC code
Identifiers
  • (1S,2R,10S,11S,14S,15S)-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.02,7.011,15]heptadec-6-en-5-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.543 Edit this at Wikidata
Chemical and physical data
FormulaC21H30O3
Molar mass330.461 g/mol g·mol−1
3D model (JSmol)
  • 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
  • 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 checkY
  • Key:ZESRJSPZRDMNHY-YFWFAHHUSA-N checkY
  (verify)

11-Deoxycorticosterone, or simply deoxycorticosterone, also known as 21-hydroxyprogesterone, is a steroid hormone produced by the adrenal gland that possesses mineralocorticoid activity and acts as a precursor to aldosterone. It has no significant glucocorticoid activity.[1] As its names indicate, 11-deoxycorticosterone can be understood as the 21-hydroxy- variant of progesterone or as the 11-deoxy- variant of corticosterone.

Biological role

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 progesterone by 21β-hydroxylase and is converted to corticosterone by 11β-hydroxylase. Corticosterone is then converted to aldosterone by aldosterone synthase.[2]

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) [3] 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).[4] At the same time it is not nearly so rigorous at retaining sodium as aldosterone,[5] more than 20 times less.[6] DOC accounts for only 1% of the sodium retention normally [7] In addition to its inherent lack of vigor there is an escape mechanism controlled by an unknown non steroid hormone [8] which overrides DOC's sodium conserving power after a few days just as aldosterone is overridden also.[9] This hormone may be the peptide hormone kallikrein,[10] which is augmented by DOC and suppressed by aldosterone.[11] If sodium becomes very high, DOC also increases urine flow.[3] DOC has about 1/20 of the sodium retaining power of aldosterone [12] and is said to be as little as one per cent of aldosterone at high water intakes.[13] Since DOC has about 1/5 the potassium excreting power of aldosterone [12] 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.[14] 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.[15] However, sodium has little effect,[16] and what effect it does have is direct.[12] Angiotensin (the blood pressure hormone) has little effect on DOC,[17] but DOC causes a rapid fall in renin, and therefore angiotensin I, the precursor of angiotensin II.[18] 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.[19] 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.[20] 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.[21] 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,[22] 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 [11] 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 [23][unreliable source?] since during dehydration, aldosterone virtually disappears [24] 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 [25] and muscle,[26] depress glycogen formation [27] and to stimulate copper containing lysyl oxidase enzyme [28] and connective tissue,[29] which attributes may be used by the body to help survive during potassium wasting intestinal diseases [30]

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.[31] 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

References

  1. ^ Costanzo, Linda S. (2007). Physiology. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7311-3.
  2. ^ Mark's Basic Medical Biochemistry: A Clinical Approach
  3. ^ a b O'Neil RG & Helmans SI (1977). "Transport characteristics of renal collecting tubules: influence of DOCA and diet". American Journal of Physiology. 233: 544–558.
  4. ^ Peterson L & Wright FS (1977) Effect of sodium intake on renal potassium excretion. American Journal of Physiology 233; 225-234.
  5. ^ Ellinghaus K (1971) Sodium and potassium balance during the administration of desoxycorticosterone in dogs with differing intakes. Pfluegers Arch. 322; 347-354.
  6. ^ From a lost reference by Brommer.
  7. ^ Ruch TC Fulton JF (1960) Medical Physiology and Biophysics. W.B. Saunders and Co., Phijl & London.
  8. ^ Pearce JW et al. (1969) Evidence for a humoral factor modifying the renal response to blood volume expansion in the rat. Can. Journal of Physiological Pharm. 47; 377-386.
  9. ^ Schacht RG et al. (1971) Renal mechanism for DOCA escape in man BulL. N.ew York Academy of Medicine 47; 1233.
  10. ^ Majima, M I Hayashi T Fujita H Ito S Nakajima (1999) Kallikrein-kinin system prevents the development of hypertension by inhibiting sodium retention. Immunopharmacology 44 issue 1+2; 145-152.
  11. ^ a b Bonner G Autenreith R Mari-Grez M Rascher W & Gross F (1981) Horm. Res. 14; 87. Cite error: The named reference "kallikrein" was defined multiple times with different content (see the help page).
  12. ^ a b c Oddie CJ et al. 1972 Plasma deoxycorticosterone levels in man with simultaneous measurement of aldosterone corticosterone, cortisol and eoxyotisol. Journal of Clinical Endocrinol. Metab. 34; 1039-54. Cite error: The named reference "DOC" was defined multiple times with different content (see the help page).
  13. ^ Desaulles P 1958 Comparison of the effects of aldosterone, cortexone and cortisol on adrenalectomized rats under various salt loads. in; International Symposium on Aldosterone (Muller AF & O'Conner, eds.) pp 29-38. Little Brown Co., Boston.
  14. ^ Bauer JH & Gauntner WC (1974) Effect of potassium chloride on plasma renin activity and plasma aldosterone during sodium restriction in normal man. Kidney International 15; Kidney Int. 15; 286.
  15. ^ Brown RD & Strott CA Liddle GW (1972) Site of stimulation of aldosterone biosynthesis by angiotensin and potassium. Journal of Clinical Investigation 51; 1413-1418.
  16. ^ Schambelan M & Biglieri EC (1972) Deoxycorticosterone production and regulation in man. Journal of Clinical Endocrinology and Metabolism 34; 695-703.
  17. ^ Brown RD & Strott CA Liddle GW (1972) Site of stimulation of aldosterone biosynthesis by angiotensin and potassium. Journal of Clinical Investigation 51; 1413-1418
  18. ^ Grekin RJ Terris JM Bohr DF 1980 Electrolyte and hormonal effects of deoxycorticosterone acetate in young pigs. Hypertension 2; 326-332.
  19. ^ Grekin RJ Terris JM Bohr DF 1980 Electrolyte and hormonal effects of deoxycorticosterone acetate in young pigs. Hypertension 2; 326-332.
  20. ^ Abbrecht PH (1972) Cardiovascular effects of chronic potassium deficiency in the dog. American Journal of Physiology 223; 555-560.
  21. ^ Rubini ME Chojnocki RF (1972) J. Clin. Nutr. 25;96.
  22. ^ Helman SI & I'Neil RG (1977) transport characteristics of renal collecting tubules:- Influence of DOCA and diet. American Journal of Physiology293; F544-558.
  23. ^ Weber CE 1998 Cortisol's purpose Medical Hypotheses 51; 289-292.
  24. ^ Merrill DC Skelton MM Cowley AWJr. (1986) Humoral control of water and electrolyte excretion during water restriction. Kidney International 29; 1152-1161.
  25. ^ Wilson, D.L. (1957) Direct effects of adrenal corticosteroids on the electrolyte content of rabbit leucocytes. American Journal of Physiology. 190: 104.
  26. ^ Tobian, L., Jr.; Binion, J.T. (1954) Artery Wall Electrolytes in Renal and DCA Hypertension. Journal of Clinical Investigation 23: 1407.
  27. ^ Bartlett, G.R>; MacKay, E.M. (1949) Insulin stimulation of glycogen formation in rat abdominal muscle. Proc. Exp. Biological Medicine 71: 493, 1949.
  28. ^ Weber, C.E. (1984) Copper response to rheumatoid arthritis. Medical Hypotheses 15: 333, 1984.
  29. ^ Pospisilova, J.; Pospisil, M. (1970) Influence of mineralocorticoids on collagen synthesis in subcutaneous granuloma in adrenalectomized and nonadrenalectomized mice. Physiologia Bohemoslovaca 19: 539,
  30. ^ Weber CE (1998) Cortisol’s purpose. Medical Hypotheses. 51: 289-292.
  31. ^ This reference has been lost. If you know it, please insert it.
  32. ^ Wambach G & Higgins JR (1979) Effect of progesterone on serum and tissue electrolyte concentration in DOCA-treated rats. Hormone Metabolism Research 11; 258-259.


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