Просмотр кода страницы Английская Википедия:11-Deoxycorticosterone

{{Английская Википедия/Панель перехода}}
{{cs1 config|name-list-style=vanc}}
{{Use dmy dates|date=December 2023}}
{{Chembox
<!-- Images -->
| ImageFile = 11-Deoxycorticosterone.svg
| ImageSize = 250
| ImageAlt =
<!-- Names -->
| IUPACName = 21-Hydroxypregn-4-ene-3,20-dione
| SystematicName = (1''S'',3a''S'',3b''S'',9a''R'',9b''S'',11a''S'')-1-(Hydroxyacetyl)-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-7''H''-cyclopenta[''a'']phenanthren-7-one
| OtherNames = Deoxycorticosterone; Desoxycortone; Deoxycortone; Cortexone; 21-Hydroxyprogesterone; 21-Hydroxy-4-pregnene-3,20-dione; Reichstein's substance Q; Kendall's desoxy compound B; NSC-11319
<!-- Sections -->
| Section1 = {{Chembox Identifiers
| CASNo = 64-85-7
| ChemSpiderID = 5932
| PubChem = 6166
| SMILES = 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
| UNII = 40GP35YQ49
| ChEBI = 16973
| ChEMBL = 1498
| IUPHAR_ligand = 2871
| StdInChI = 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
| StdInChIKey = ZESRJSPZRDMNHY-YFWFAHHUSA-N
  }}
| Section2 = {{Chembox Properties
| Formula = C<sub>21</sub>H<sub>30</sub>O<sub>3</sub>
| MolarMass = 330.461 g/mol
| Appearance =
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| Section3 = {{Chembox Hazards
| MainHazards =
| FlashPt =
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| Section6 = {{Chembox Pharmacology
| ATCCode_prefix = H02
| ATCCode_suffix = AA03
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}}

'''11-Deoxycorticosterone''' ('''DOC'''), or simply '''deoxycorticosterone''', also known as '''21-hydroxyprogesterone''', as well as '''desoxycortone''' ([[International Nonproprietary Name|INN]]), '''deoxycortone''', and '''cortexone''',{{sfn|Buckingham|MacDonald|Heilbron|1995}}{{sfn|Swiss Pharmaceutical Society|2011}} is a [[steroid hormone]] produced by the [[adrenal gland]] that possesses [[mineralocorticoid]] activity and acts as a [[precursor (chemistry)|precursor]] to [[aldosterone]].{{sfn| Costanzo| 2014}} It is an active (Na+-retaining) mineralocorticoid.<ref name="Harper's-Illustrated Biochemistry">Harper's Illustrated Biochemistry 30th Edition</ref> As its names indicate, {{nowrap|11-deoxycorticosterone}} can be understood as the 21-[[hydroxyl|hydroxy]]-variant of [[progesterone]] or as the 11-[[deoxy]]-variant of [[corticosterone]].

''DOCA'' is the abbreviation for the [[ester]] 11-deoxycorticosterone [[acetate]].<ref name="pmid28851937">{{cite journal | vauthors = Wang D, Luo Y, Myakala K, Orlicky DJ, Dobrinskikh E, Wang X, Levi M | title = Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 9793 | date = August 2017 | pmid = 28851937 | pmc = 5574886 | doi = 10.1038/s41598-017-09470-0 | bibcode = 2017NatSR...7.9793W }}</ref>

==Biological activity==
DOC is a potent [[mineralocorticoid]] but is virtually devoid of [[glucocorticoid]] activity.<ref name="pmid6274900">{{cite journal |vauthors=Lan NC, Graham B, Bartter FC, Baxter JD |title=Binding of steroids to mineralocorticoid receptors: implications for in vivo occupancy by glucocorticoids |journal=J Clin Endocrinol Metab |volume=54 |issue=2 |pages=332–42 |date=February 1982 |pmid=6274900 |doi=10.1210/jcem-54-2-332 |url=}}</ref><ref name="pmid15947887">{{cite journal |vauthors=Funder JW |title=Mineralocorticoid receptors: distribution and activation |journal=Heart Fail Rev |volume=10 |issue=1 |pages=15–22 |date=January 2005 |pmid=15947887 |doi=10.1007/s10741-005-2344-2 |s2cid=1423344 |url=}}</ref><ref name="Goodman-2010">{{Cite book |last= Goodman |first=H. Maurice | name-list-style = vanc |url=https://books.google.com/books?id=gjpi2MYVKGAC&pg=PA64 |title=Basic Medical Endocrinology |date=28 July 2010 |publisher=Academic Press |isbn=978-0-08-092055-9 |pages=64}}</ref> However, 11β-hydroxylation of DOC produces [[corticosterone]] and confers glucocorticoid activity, along with 10-fold reduced mineralocorticoid activity.<ref name="Goodman-2010" /> 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.<ref name="Springer2013">{{Cite book |url=https://books.google.com/books?id=BLXoCAAAQBAJ&pg=PA610 |title=The Adrenocortical Hormones: Their Origin · Chemistry, Physiology, and Pharmacology |date=27 November 2013 |publisher=Springer Science & Business Media |isbn=978-3-642-88385-9 |pages=610}}</ref> However, it has no such activity when applied directly to the uterine mucosa of mice.<ref name="Springer2013" /> The discrepancy may be related to the fact that DOC can be converted into progesterone ''[[in vivo]]''.<ref name="Springer2013" />

==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 [[Steroid 11-beta-hydroxylase|11β-hydroxylase]]. Corticosterone is then converted to aldosterone by [[aldosterone synthase]].{{sfn|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) {{sfn|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).{{sfn| Peterson| Wright| 1977}} At the same time it is not nearly so rigorous at retaining sodium as aldosterone,{{sfn|Ellinghaus|1971}} more than 20 times less. DOC accounts for only 1% of the sodium retention normally {{sfn|Ruch| Fulton| 1960}} In addition to its inherent lack of vigor there is an escape mechanism controlled by an unknown non steroid hormone {{sfn| Pearce| Sonnenberg| Veress| Ackermann| 1969}} which overrides DOC's sodium conserving power after a few days just as aldosterone is overridden also.{{sfn|Schacht |Lowenstein
| Baldwin| 1971}} This hormone may be the peptide hormone [[kallikrein]],{{sfn| Majima| Hayashi| Fujita| Ito | 1999}} which is augmented by DOC and suppressed by aldosterone.{{sfn|Bönner|Autenrieth|Marin-Grez|Rascher|1981}} If sodium becomes very high, DOC also increases urine flow.{{sfn|O'Neil |Helman| 1977}} DOC has about 1/20 of the sodium retaining power of aldosterone,{{sfn|Oddie | Coghlan| Scoggins| 1972}} and is said to be as little as one per cent of aldosterone at high water intakes.{{sfn| Desaulles| 1958}} Since DOC has about 1/5 the potassium excreting power of aldosterone,{{sfn|Oddie | Coghlan| Scoggins| 1972}} 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.{{sfn|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.

DOC has a similar feedback with respect to potassium as aldosterone. A rise in serum potassium causes a rise in DOC secretion.{{sfn| Brown| Strott| Liddle| 1972}} However, sodium has little effect,{{sfn| Schambelan| Biglieri|1972}} and what effect it does have is direct.{{sfn|Oddie | Coghlan| Scoggins| 1972}} [[Angiotensin]] (the blood pressure hormone) has little effect on DOC,{{sfn| Brown| Strott| Liddle| 1972}} but DOC causes a rapid fall in [[renin]], and therefore angiotensin I, the precursor of [[angiotensin II]].{{sfn| 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.{{sfn| 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.{{sfn|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.{{sfn| 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.

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,{{sfn| 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,{{sfn|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 may be to give the immune system control over the electrolyte regulation during diarrhea since during [[dehydration]], aldosterone virtually disappears {{sfn| 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 {{sfn| Wilson| 1957}} and muscle,{{sfn| Tobian| Binion| 1954}} depress glycogen formation {{sfn| Bartlett| MacKay| 1949}} and to stimulate copper containing lysyl oxidase enzyme  and connective tissue,{{sfn| 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.{{sfn| Wambach| Higgins|1979}}

==Additional images==
<gallery>
File:Steroidogenesis.svg|[[Steroidogenesis]]
File:Corticosterone-2D-skeletal.svg|[[Corticosterone]]
</gallery>

== See also ==
* [[11-Deoxycortisol]]
* [[17α-Hydroxyprogesterone]]
* [[Corticosterone]]
* [[Congenital adrenal hyperplasia]]

== References ==
{{Reflist|30em}}

==Sources==
{{refbegin|30em}}
* {{cite journal | vauthors = Abbrecht PH | title = Cardiovascular effects of chronic potassium deficiency in the dog | journal = The American Journal of Physiology | volume = 223 | issue = 3 | pages = 555–60 | date = September 1972 | pmid = 4403425 | doi = 10.1152/ajplegacy.1972.223.3.555 }}
* {{cite journal | vauthors = Bartlett GR, MacKay EM | title = Insulin stimulation of glycogen formation in rat abdominal muscle | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 71 | issue = 3 | pages = 493–5 | date = July 1949 | pmid = 18136520 | doi = 10.3181/00379727-71-17234 | s2cid = 31824669 }}
* {{cite journal | vauthors = Bauer JH, Gauntner WC | title = Effect of potassium chloride on plasma renin activity and plasma aldosterone during sodium restriction in normal man | journal = Kidney International | volume = 15 | issue = 3 | pages = 286–93 | date = March 1979 | pmid = 513492 | doi = 10.1038/ki.1979.37 | doi-access = free }}
* {{cite journal | vauthors = Bönner G, Autenrieth R, Marin-Grez M, Rascher W, Gross F | title = Effects of sodium loading, desoxycorticosterone acetate, and corticosterone on urinary kallikrein excretion | journal = Hormone Research | volume = 14 | issue = 2 | pages = 87–94 | date = 1981 | pmid = 6912177 | doi = 10.1159/000179365 }}
* {{cite journal | vauthors = Brown RD, Strott CA, Liddle GW | title = Site of stimulation of aldosterone biosynthesis by angiotensin and potassium | journal = The Journal of Clinical Investigation | volume = 51 | issue = 6 | pages = 1413–8 | date = June 1972 | pmid = 4336939 | pmc = 292278 | doi = 10.1172/JCI106937 }}
* {{Cite encyclopedia |year=1995 |title=Dictionary of Organic Compounds |publisher=CRC Press | veditors = Buckingham J, MacDonald F, Heilbron I |edition=6th |volume=1 |isbn=978-0412540905 }}
* {{Cite book |last=Costanzo |first=Linda S. | name-list-style = vanc |title=Physiology |work=Board Review Series (BRS) |publisher=Lippincott Williams & Wilkins |year=2014 |isbn=978-1469832005 |edition=International }}
* {{Cite conference | vauthors = Desaulles P |date=1958 | veditors = Muller AF, O'Connor CM |title=Comparison of the effects of aldosterone, cortexone and cortisol on adrenalectomized rats under various salt loads |conference=An International Symposium on Aldosterone, Geneva 1957 |location=Boston |publisher=Little Brown Co |pages=29–38 |oclc=14594852 }}
* {{cite journal | vauthors = Ellinghaus K | title = Sodium and potassium balance during the administration of desoxycorticosterone in dogs with differing dietary sodium intakes | journal = Pflügers Archiv | volume = 322 | issue = 4 | pages = 347–54 | date = 1971 | pmid = 5100181 | doi = 10.1007/BF00587752 | s2cid = 1968289 }}
* {{cite journal | vauthors = Grekin RJ, Terris JM, Bohr DF | title = Electrolyte and hormonal effects of deoxycorticosterone acetate in young pigs | journal = Hypertension | volume = 2 | issue = 3 | pages = 326–32 | date = 1980 | pmid = 6993359 | doi = 10.1161/01.HYP.2.3.326 | doi-access = free }}
* {{Cite book |last1=Lieberman |first1=Michael A. |last2=Marks |first2=Allan |last3=Peet |first3=Alisa | name-list-style = vanc |title=Marks' Basic Medical Biochemistry: A Clinical Approach |publisher=Lippincott Williams and Wilkins |others=Matthew Chansky (Illustrator) |year=2012 |isbn=978-1608315727 |edition=4th }}
* {{cite journal | vauthors = Majima M, Hayashi I, Fujita T, Ito H, Nakajima S, Katori M | title = Facilitation of renal kallikrein-kinin system prevents the development of hypertension by inhibition of sodium retention | journal = Immunopharmacology | volume = 44 | issue = 1–2 | pages = 145–52 | date = October 1999 | pmid = 10604538 | doi = 10.1016/S0162-3109(99)00086-7 }}
* {{cite journal | vauthors = Merrill DC, Skelton MM, Cowley AW | title = Humoral control of water and electrolyte excretion during water restriction | journal = Kidney International | volume = 29 | issue = 6 | pages = 1152–61 | date = June 1986 | pmid = 3528610 | doi = 10.1038/ki.1986.121 | doi-access = free }}
* {{cite journal | vauthors = Oddie CJ, Coghlan JP, Scoggins BA | title = Plasma desoxycorticosterone levels in man with simultaneous measurement of aldosterone, corticosterone, cortisol and 11-deoxycortisol | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 34 | issue = 6 | pages = 1039–54 | date = June 1972 | pmid = 4336456 | doi = 10.1210/jcem-34-6-1039 }}
* {{cite journal | vauthors = O'Neil RG, Helman SI | title = Transport characteristics of renal collecting tubules: influences of DOCA and diet | journal = The American Journal of Physiology | volume = 233 | issue = 6 | pages = F544-58 | date = December 1977 | pmid = 596453 | doi = 10.1152/ajprenal.1977.233.6.F544 }}
* {{cite journal | vauthors = Pearce JW, Sonnenberg H, Veress AT, Ackermann U | title = Evidence for a humoral factor modifying the renal response to blood volume expansion in the rat | journal = Canadian Journal of Physiology and Pharmacology | volume = 47 | issue = 4 | pages = 377–86 | date = April 1969 | pmid = 5772633 | doi = 10.1139/y69-066 }}
* {{cite journal | vauthors = Peterson LN, Wright FS | title = Effect of sodium intake on renal potassium excretion | journal = The American Journal of Physiology | volume = 233 | issue = 3 | pages = F225-34 | date = September 1977 | pmid = 910918 | doi = 10.1152/ajprenal.1977.233.3.F225 }}
* {{cite journal | vauthors = Pospísilová J, Pospísil M | title = Influence of mineralocorticoids on collagen synthesis in subcutaneous granuloma in adrenalectomized and non-adrenalectomized mice | journal = Physiologia Bohemoslovaca | volume = 19 | issue = 6 | pages = 539–43 | date = 1970 | pmid = 4251388 }}
* {{cite journal | vauthors = Rubini ME, Chojnacki RE | title = Principles of parenteral therapy | journal = The American Journal of Clinical Nutrition | volume = 25 | issue = 1 | pages = 96–113 | date = January 1972 | pmid = 5007603 | doi = 10.1093/ajcn/25.1.96 | doi-access = free }}
* {{Cite book |title=Medical Physiology and Biophysics |date=1960 |publisher=W. B. Saunders and Co. | veditors = Ruch T, Fulton JF }}
* {{cite journal | vauthors = Schacht RG, Lowenstein J, Baldwin DS | title = Renal mechanism for DOCA escape in man | journal = Bulletin of the New York Academy of Medicine | volume = 47 | issue = 10 | pages = 1233 | date = October 1971 | pmid = 5286466 }}
* {{cite journal | vauthors = Schambelan M, Biglieri EG | title = Deoxycorticosterone production and regulation in man | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 34 | issue = 4 | pages = 695–703 | date = April 1972 | pmid = 4335105 | doi = 10.1210/jcem-34-4-695 }}
* {{Cite book |last=Swiss Pharmaceutical Society |title=Index Nominum: International Drug Directory |date=2011 |publisher=Wissenschaftliche Verlag |isbn=978-3804750531 |edition=20th }}
* {{cite journal | vauthors = Tobian L, Binion J | title = Artery wall electrolytes in renal and DCA hypertension | journal = The Journal of Clinical Investigation | volume = 33 | issue = 10 | pages = 1407–14 | date = October 1954 | pmid = 13201647 | pmc = 1072561 | doi = 10.1172/JCI103018 }}
* {{cite journal | vauthors = Wambach G, Higgins JR | title = Effect of progesterone on serum and tissue electrolyte concentration in doca-treated rats | journal = Hormone and Metabolic Research | volume = 11 | issue = 3 | pages = 258–9 | date = March 1979 | pmid = 447212 | doi = 10.1055/s-0028-1095777 | s2cid = 36911377 }}
* {{cite journal | vauthors = Wilson DL | title = Direct effects of adrenal cortical steroids on the electrolyte content of rabbit leucocytes | journal = The American Journal of Physiology | volume = 190 | issue = 1 | pages = 104–8 | date = July 1957 | pmid = 13458419 | doi = 10.1152/ajplegacy.1957.190.1.104 | doi-access =  }}
{{refend}}

{{Endogenous steroids}}
{{Mineralocorticoid receptor modulators}}
{{Progesterone receptor modulators}}
{{Glycine receptor modulators}}

{{DEFAULTSORT:Deoxycorticosterone, 11-}}
[[Category:Glycine receptor antagonists]]
[[Category:Mineralocorticoids]]
[[Category:Pregnanes]]
[[Category:Progestogens]]
[[Category:Steroid hormones]]
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