deoxycorticosterone

デオキシコルチコステロン DOC

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/23 22:18:01」(JST)

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11-Deoxycorticosterone

Systematic (IUPAC) name
(1S,2R,10S,11S,14S,15S)-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.02,7.011,15]heptadec-6-en-5-one
Clinical data
Pregnancy cat.	?
Legal status	?
Identifiers
CAS number	64-85-7 Y 56-47-3 (acetate ester)
ATC code	H02AA03
PubChem	CID 6166
ChemSpider	5932 Y
UNII	40GP35YQ49 Y
ChEBI	CHEBI:16973 Y
ChEMBL	CHEMBL1498 Y
Synonyms	11-Desoxycorticosterone; Deoxycorticosterone; 21-Hydroxyprogesterone; Cortexone; Deoxycortone; Desoxycortone; DOC
Chemical data
Formula	C21H30O3
Mol. mass	330.461 g/mol
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
InChI 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 Y Key:ZESRJSPZRDMNHY-YFWFAHHUSA-N Y
Y (what is this?)  (verify)

11-Deoxycorticosterone (DOC), 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. 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

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.

Most of the 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.

Additional images

• Steroidogenesis

• Corticosterone

See also

• Cortodoxone (11-Deoxycortisol)
• 17-Hydroxyprogesterone
• Corticosterone

References

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 見かけの鉱質コルチコイド過剰（AME）症候群（長期甘草摂取を含む） apparent mineralocorticoid excess syndromes including chronic licorice ingestion
• 2. 副腎ステロイド生合成 adrenal steroid biosynthesis
• 3. 先天性副腎過形成の稀な原因 uncommon causes of congenital adrenal hyperplasia
• 4. 11βヒドロキシラーゼ欠損症による先天性副腎過形成 congenital adrenal hyperplasia due to 11 beta hydroxylase deficiency
• 5. 低カリウム血症を合併した高血圧症へのアプローチ approach to the patient with hypertension and hypokalemia

English Journal

• Corticosteroids stimulate the amphibious behavior in mudskipper: Potential role of mineralocorticoid receptors in teleost fish.

• Sakamoto T, Mori C, Minami S, Takahashi H, Abe T, Ojima D, Ogoshi M, Sakamoto H.SourceUshimado Marine Institute, Faculty of Science, Okayama University, Ushimado, Setouchi 701-4303, Japan.
• Physiology & behavior.Physiol Behav.2011 Oct 24;104(5):923-8. Epub 2011 Jun 12.
• It has long been held that cortisol, a glucocorticoid in many vertebrates, carries out both glucocorticoid and mineralocorticoid actions in teleost fish. However, 11-deoxycorticosterone (DOC) has been identified as a specific endogenous ligand for the teleostean mineralocorticoid receptor (MR). Furt
• PMID 21683725

• The mislabelling of deoxycorticosterone: making sense of corticosteroid structure and function.

• Vinson GP.SourceSchool of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK.
• The Journal of endocrinology.J Endocrinol.2011 Oct;211(1):3-16. Epub 2011 Jun 29.
• Over the 70 or so years since their discovery, there has been continuous interest and activity in the field of corticosteroid functions. However, despite major advances in the characterisation of receptors and coregulators, in some ways we still lack clear insight into the mechanism of receptor acti
• PMID 21715433

Japanese Journal

• Pharmacology in Health Foods:Improvement of Vascular Endothelial Function by French Maritime Pine Bark Extract (Flavangenol)

• Ohkita Mamoru,Kiso Yoshinobu,Matsumura Yasuo
• Journal of Pharmacological Sciences 115(4), 461-465, 2011
• … suppresses nuclear factor-kappa B (NF-κB) activation and the subsequent various NF-κB–induced gene expressions such as those of adhesion molecules and endothelin-1 in cultured vascular endothelial cells and that the antihypertensive effect of Flavangenol on deoxycorticosterone acetate–salt hypertensive rats is attributable to both its antioxidative property–related protective effects against endothelial dysfunction and the endothelium-dependent vasorelaxant effect, which is mediated by endothelial nitric oxide synthase …
• NAID 130000663509

• SM-368229, a Novel Selective and Potent Non-steroidal Mineralocorticoid Receptor Antagonist With Strong Urinary Na+ Excretion Activity

• Nariai Tetsuro,Fujita Katsuya,Mori Masaya,Katayama Seiji,Hori Seiji,Matsui Kazuki
• Journal of Pharmacological Sciences 115(3), 346-353, 2011
• … SM-368229 dose-dependently increased urinary Na+/K+ ratio with an ED50 value of 5.6 mg/kg in adrenalectomized rats treated with deoxycorticosterone acetate, and its efficacy was superior to that of SPI (ED50 = 14 mg/kg) or EPL (ED50 = 147 mg/kg). …
• NAID 130000663397

Related Links

• 11-Deoxycorticosterone - Wikipedia, the free 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 ...

Related Pictures

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★リンクテーブル★

リンク元	「副腎皮質ホルモン」「デオキシコルチコステロン」「DOCA」「desoxycorticosterone」「DOC」
拡張検索	「deoxycorticosterone acetate」「11-deoxycorticosterone」

「副腎皮質ホルモン」

　　[★]

英

adrenocortical hormone

同

副腎皮質ステロイド adrenocorticoids

関

副腎皮質刺激ホルモン放出ホルモン、副腎皮質刺激ホルモン

ステロイド

関

副腎、副腎皮質、ステロイド、コルチコステロイド、ステロイドホルモン、コルチコイド。副腎皮質ホルモン剤

• 図：SP.891(組織),892(構造式)
• 副腎皮質の球状層、索状層、網状層で合成される

種類(主要なもののみ)

• 電解質コルチコイド

球状層から分泌される。アルドステロン

• 糖質コルチコイド

索状層から分泌される。コルチゾール

• 副腎アンドロジェン

網状層から分泌される。アンドロステンジオン

コレステロール cholesterol
↓CYP11A1
プレグネノロン pregnenolone	－－→ CYP17 17α-hydroxylase	17α-ヒドロキシプレグネノロン 17α-hydroxypregnenolone	－－→ CYP17 17α-hydroxylase	デヒドロエピアンドロステロン dehydroepiandrosterone DHEA
↓3β-HSD 3β-hydroxysteroid dehydrogenase		↓3β-HSD		↓3β-HSD
プロゲステロン progesterone	－－→ CYP17 17α-hydroxylase	17α-ヒドロキシプロゲステロン 17α-hydroxyprogesterone	－－→ CYP17 17α-hydroxylase	アンドロステンジオン androstenedione Δ4androstene-3,17-dion
↓CYP21 21-hydroxylase		↓CYP21 21-hydroxylase
デオキシコルチコステロン deoxycorticosterone		11-デオキシコルチゾール 11-deoxycortisol
↓CYP11B2　11β-hydroxylase		↓CYP11B1　11β-hydroxylase
コルチコステロン corticosterone		コルチゾール cortisol
↓CYP11B2 18-hydroxylase
18-ヒドロキシコルチコステロン 18-hydroxycorticosterone
↓CYP11B2 18-hydroxydehydrogenase
アルドステロン aldosterone
球状増 zona glomerulosa		索状層 zona fasciculata		網状層 zona reticularis

臨床関連

• 副腎皮質ホルモン過多：クッシング症候群
• 副腎皮質ホルモン欠乏：アジソン病
• 副腎皮質ホルモン合成異常：先天性副腎過形成

21-hydroxylaseが正常に機能しないことにより生じる (L.320)

薬理学

• 副腎皮質ホルモン製剤

副腎皮質から分泌されるホルモン (SP.895)

名称		血漿濃度 (ng/ml)	1日分泌量 (mg/day)
糖質コルチコイド	コルチゾール	40～180	15～20
	コルチコステロン	2～6	2～5
鉱質コルチコイド	アルドステロン	0.05～0.20	0.05～0.15
	11-DOC	0.05～0.30	0.10～0.20
副腎アンドロジェン	DHEA	2～8	7～15
	DHEA-S	1～4
	アンドロステンジオン	1～2	2～3

「デオキシコルチコステロン」

　　[★]

英

deoxycorticosterone DOC

関

11-デオキシコルチコステロン 11-deoxycorticosterone

• 鉱質コルチコイド作用を有するが、その効力はアルドステロンの1/25である。
• 11-ヒドロキシラーゼ欠損症ではデオキシコルチコステロンの蓄積により高血圧を呈する。

「DOCA」

　　[★]

• 酢酸デオキシコルチコステロン

関

deoxycorticosterone、deoxycorticosterone acetate、desoxycorticosterone、desoxycortone

「desoxycorticosterone」

　　[★]

デスオキシコルチコステロン、デゾキシコルチコステロン

関

deoxycorticosterone、desoxycortone、DOCA

「DOC」

　　[★] デオキシコルチコステロン deoxycorticosterone

関

11-デオキシコルチコステロン

「deoxycorticosterone acetate」

　　[★]

・酸デオキシコルチコステロン

関

DOCA

「11-deoxycorticosterone」

　　[★] 11-デオキシコルチコステロン