11-Deoxycorticosterone

vanc December 2023 11-Deoxycorticosterone.svg skin-invert-image 250 21-Hydroxypregn-4-ene-3,20-dione (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 Deoxycorticosterone; Desoxycortone; Deoxycortone; Cortexone; 21-Hydroxyprogesterone; 21-Hydroxy-4-pregnene-3,20-dione; Reichstein's substance Q; Kendall's desoxy compound B; NSC-11319 64-85-7 5932 6166 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 40GP35YQ49 16973 1498 2871 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 ZESRJSPZRDMNHY-YFWFAHHUSA-N C21H30O3 330.468 g/mol H02 AA03 11-Deoxycorticosterone (DOC), or simply deoxycorticosterone, also known as 21-hydroxyprogesterone, as well as desoxycortone (INN), deoxycortone, and cortexone,Buckingham MacDonald Heilbron 1995Swiss Pharmaceutical Society 2011 is a steroid hormone produced by the adrenal gland that possesses mineralocorticoid activity and acts as a precursor to aldosterone. Costanzo 2014 It is an active (Na+-retaining) mineralocorticoid.Harper's Illustrated Biochemistry 30th Edition 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. Wang D, Luo Y, Myakala K, Orlicky DJ, Dobrinskikh E, Wang X, Levi M Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats Scientific Reports 7 1 9793 August 2017 28851937 5574886 10.1038/s41598-017-09470-0 free 2017NatSR...7.9793W Biological activity DOC is a potent mineralocorticoid but is virtually devoid of glucocorticoid activity.Lan NC, Graham B, Bartter FC, Baxter JD Binding of steroids to mineralocorticoid receptors: implications for in vivo occupancy by glucocorticoids J Clin Endocrinol Metab 54 2 332–42 February 1982 6274900 10.1210/jcem-54-2-332 Funder JW Mineralocorticoid receptors: distribution and activation Heart Fail Rev 10 1 15–22 January 2005 15947887 10.1007/s10741-005-2344-2 1423344 Goodman H. Maurice https://books.google.com/books?id=gjpi2MYVKGAC&pg=PA64 Basic Medical Endocrinology 28 July 2010 Academic Press 978-0-08-092055-9 64 However, 11β-hydroxylation of DOC produces corticosterone and confers glucocorticoid activity, along with 10-fold reduced mineralocorticoid activity. 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.https://books.google.com/books?id=BLXoCAAAQBAJ&pg=PA610 The Adrenocortical Hormones: Their Origin · Chemistry, Physiology, and Pharmacology 27 November 2013 Springer Science & Business Media 978-3-642-88385-9 610 However, it has no such activity when applied directly to the uterine mucosa of mice. The discrepancy may be related to the fact that DOC can be converted into progesterone in vivo. 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.Lieberman Marks Peet 2012 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)O'Neil Helman 1977 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). Peterson Wright 1977 At the same time it is not nearly so rigorous at retaining sodium as aldosterone,Ellinghaus 1971 more than 20 times less. DOC accounts for only 1% of the sodium retention normallyRuch Fulton 1960 In addition to its inherent lack of vigor there is an escape mechanism controlled by an unknown non steroid hormone Pearce Sonnenberg Veress Ackermann 1969 which overrides DOC's sodium conserving power after a few days just as aldosterone is overridden also.Schacht Lowenstein Baldwin 1971 This hormone may be the peptide hormone kallikrein, Majima Hayashi Fujita Ito 1999 which is augmented by DOC and suppressed by aldosterone.Bönner Autenrieth Marin-Grez Rascher 1981 If sodium becomes very high, DOC also increases urine flow.O'Neil Helman 1977 DOC has about 1/20 of the sodium retaining power of aldosterone,Oddie Coghlan Scoggins 1972 and is said to be as little as one per cent of aldosterone at high water intakes. Desaulles 1958 Since DOC has about 1/5 the potassium excreting power of aldosterone,Oddie Coghlan Scoggins 1972 it probably requires 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.Bauer Gauntner 1979 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.June 2024 DOC has a similar feedback with respect to potassium as aldosterone. A rise in serum potassium causes a rise in DOC secretion. Brown Strott Liddle 1972 However, sodium has little effect, Schambelan Biglieri 1972 and what effect it does have is direct.Oddie Coghlan Scoggins 1972 Angiotensin (the blood pressure hormone) has little effect on DOC, Brown Strott Liddle 1972 but DOC causes a rapid fall in renin, and therefore angiotensin I, the precursor of angiotensin II. Grekin Terris Bohr 1980 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. Grekin Terris Bohr 1980 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.Abbrecht 1972 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. Rubini Chojnacki 1972 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.June 2024 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, O'Neil Helman 1977 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,Bönner Autenrieth Marin-Grez Rascher 1981 is also supportive of the above concept. ACTH has more effect on DOC than it does on aldosterone. This difference may exist to give the immune system control over the electrolyte regulation during diarrhea since during dehydration, aldosterone virtually disappears Merrill Skelton Cowley 1986 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 Wilson 1957 and muscle, Tobian Binion 1954 depress glycogen formation Bartlett MacKay 1949 and to stimulate copper containing lysyl oxidase enzyme and connective tissue, Pospísilová Pospísil 1970 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. Wambach Higgins 1979 Additional images See also 11-Deoxycortisol 17α-Hydroxyprogesterone Corticosterone Congenital adrenal hyperplasia References 30em Sources 30em Abbrecht PH Cardiovascular effects of chronic potassium deficiency in the dog The American Journal of Physiology 223 3 555–60 September 1972 4403425 10.1152/ajplegacy.1972.223.3.555 Bartlett GR, MacKay EM Insulin stimulation of glycogen formation in rat abdominal muscle Proceedings of the Society for Experimental Biology and Medicine 71 3 493–5 July 1949 18136520 10.3181/00379727-71-17234 31824669 Bauer JH, Gauntner WC Effect of potassium chloride on plasma renin activity and plasma aldosterone during sodium restriction in normal man Kidney International 15 3 286–93 March 1979 513492 10.1038/ki.1979.37 free Bönner G, Autenrieth R, Marin-Grez M, Rascher W, Gross F Effects of sodium loading, desoxycorticosterone acetate, and corticosterone on urinary kallikrein excretion Hormone Research 14 2 87–94 1981 6912177 10.1159/000179365 Brown RD, Strott CA, Liddle GW Site of stimulation of aldosterone biosynthesis by angiotensin and potassium The Journal of Clinical Investigation 51 6 1413–8 June 1972 4336939 292278 10.1172/JCI106937 1995 Dictionary of Organic Compounds CRC Press Buckingham J, MacDonald F, Heilbron I 6th 1 978-0412540905 Costanzo Linda S. Physiology Board Review Series (BRS) Lippincott Williams & Wilkins 2014 978-1469832005 International Desaulles P 1958 Muller AF, O'Connor CM Comparison of the effects of aldosterone, cortexone and cortisol on adrenalectomized rats under various salt loads An International Symposium on Aldosterone, Geneva 1957 Boston Little Brown Co 29–38 14594852 Ellinghaus K Sodium and potassium balance during the administration of desoxycorticosterone in dogs with differing dietary sodium intakes Pflügers Archiv 322 4 347–54 1971 5100181 10.1007/BF00587752 1968289 Grekin RJ, Terris JM, Bohr DF Electrolyte and hormonal effects of deoxycorticosterone acetate in young pigs Hypertension 2 3 326–32 1980 6993359 10.1161/01.HYP.2.3.326 free Lieberman Michael A. Marks Allan Peet Alisa Marks' Basic Medical Biochemistry: A Clinical Approach Lippincott Williams and Wilkins Matthew Chansky (Illustrator) 2012 978-1608315727 4th Majima M, Hayashi I, Fujita T, Ito H, Nakajima S, Katori M Facilitation of renal kallikrein-kinin system prevents the development of hypertension by inhibition of sodium retention Immunopharmacology 44 1–2 145–52 October 1999 10604538 10.1016/S0162-3109(99)00086-7 Merrill DC, Skelton MM, Cowley AW Humoral control of water and electrolyte excretion during water restriction Kidney International 29 6 1152–61 June 1986 3528610 10.1038/ki.1986.121 free Oddie CJ, Coghlan JP, Scoggins BA Plasma desoxycorticosterone levels in man with simultaneous measurement of aldosterone, corticosterone, cortisol and 11-deoxycortisol The Journal of Clinical Endocrinology and Metabolism 34 6 1039–54 June 1972 4336456 10.1210/jcem-34-6-1039 O'Neil RG, Helman SI Transport characteristics of renal collecting tubules: influences of DOCA and diet The American Journal of Physiology 233 6 F544-58 December 1977 596453 10.1152/ajprenal.1977.233.6.F544 Pearce JW, Sonnenberg H, Veress AT, Ackermann U Evidence for a humoral factor modifying the renal response to blood volume expansion in the rat Canadian Journal of Physiology and Pharmacology 47 4 377–86 April 1969 5772633 10.1139/y69-066 Peterson LN, Wright FS Effect of sodium intake on renal potassium excretion The American Journal of Physiology 233 3 F225-34 September 1977 910918 10.1152/ajprenal.1977.233.3.F225 Pospísilová J, Pospísil M Influence of mineralocorticoids on collagen synthesis in subcutaneous granuloma in adrenalectomized and non-adrenalectomized mice Physiologia Bohemoslovaca 19 6 539–43 1970 4251388 Rubini ME, Chojnacki RE Principles of parenteral therapy The American Journal of Clinical Nutrition 25 1 96–113 January 1972 5007603 10.1093/ajcn/25.1.96 free Medical Physiology and Biophysics 1960 W. B. Saunders and Co. Ruch T, Fulton JF Schacht RG, Lowenstein J, Baldwin DS Renal mechanism for DOCA escape in man Bulletin of the New York Academy of Medicine 47 10 1233 October 1971 5286466 Schambelan M, Biglieri EG Deoxycorticosterone production and regulation in man The Journal of Clinical Endocrinology and Metabolism 34 4 695–703 April 1972 4335105 10.1210/jcem-34-4-695 Swiss Pharmaceutical Society Index Nominum: International Drug Directory 2011 Wissenschaftliche Verlag 978-3804750531 20th Tobian L, Binion J Artery wall electrolytes in renal and DCA hypertension The Journal of Clinical Investigation 33 10 1407–14 October 1954 13201647 1072561 10.1172/JCI103018 Wambach G, Higgins JR Effect of progesterone on serum and tissue electrolyte concentration in doca-treated rats Hormone and Metabolic Research 11 3 258–9 March 1979 447212 10.1055/s-0028-1095777 36911377 Wilson DL Direct effects of adrenal cortical steroids on the electrolyte content of rabbit leucocytes The American Journal of Physiology 190 1 104–8 July 1957 13458419 10.1152/ajplegacy.1957.190.1.104 Category:Glycine receptor antagonists Category:Mineralocorticoids Category:Pregnanes Category:Progestogens Category:Steroid hormones