11-Dehydrocorticosterone
(Synonyms: 11-去氫皮質甾酮,11-DHC) 目录号 : GC48710An endogenous mineralocorticoid
Cas No.:72-23-1
Sample solution is provided at 25 µL, 10mM.
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11-Dehydrocorticosterone is an endogenous mineralocorticoid.[1],[2],[3] It increases Na+/K+-ATPase mRNA expression in vascular smooth muscle cells and inhibits aldosterone action in B. marinus toad bladder tissue in a concentration-dependent manner.[1],[2] 11-Dehydrocorticosterone decreases the sodium/creatine ratio and increases the potassium/creatine ratio in rat urine in a dose-dependent manner in a model of 11β-hydroxysteroid dehydrogenase inhibition induced by carbenoxolone .[3] Chronic administration 11-dehydrocorticosterone increases plasma glucocorticoids levels, body weight gain, and adiposity, as well as induces insulin resistance in mice.[4]
Reference:
[1].Muto, S., Nemoto, J., Ebata, S., et al.Corticosterone and 11-dehydrocorticosterone stimulate Na,K-ATPase gene expression in vascular smooth muscle cellsKidney Int.54(2)492-508(1998)
[2].Brem, A.S., Matheson, K.L., Barnes, J.L., et al.11-Dehydrocorticosterone, a glucocorticoid metabolite, inhibits aldosterone action in toad bladderAm. J. Physiol.261(5)F873-F879(1991)
[3].Souness, G.W., and Morris, D.J.11-Dehydrocorticosterone in the presence of carbenoxolone is a more potent sodium retainer than corticosteroneSteroids58(1)24-28(1993)
[4].Harno, E., Cottrell, E.C., Keevil, B.G., et al.11-Dehydrocorticosterone causes metabolic syndrome, which is prevented when 11β-HSD1 is knocked out in livers of male miceEndocrinology154(10)3599-3609(2013)
| Cas No. | 72-23-1 | SDF | |
| 别名 | 11-去氫皮質甾酮,11-DHC | ||
| 化学名 | 21-hydroxy-pregn-4-ene-3,11,20-trione | ||
| Canonical SMILES | C[C@@]12[C@]3([H])[C@](CCC1=CC(CC2)=O)([H])[C@@]4([H])[C@](CC3=O)([C@H](CC4)C(CO)=O)C | ||
| 分子式 | C21H28O4 | 分子量 | 344.4 |
| 溶解度 | DMF: 30 mg/mL; DMSO: 30 mg/mL; Ethanol: 5 mg/mL | 储存条件 | -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9036 mL | 14.518 mL | 29.036 mL |
| 5 mM | 0.5807 mL | 2.9036 mL | 5.8072 mL |
| 10 mM | 0.2904 mL | 1.4518 mL | 2.9036 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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2.
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11β-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action
Physiol Rev 2013 Jul;93(3):1139-206.PMID:23899562DOI:10.1152/physrev.00020.2012.
Glucocorticoid action on target tissues is determined by the density of "nuclear" receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-Dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental "programming." The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.
11-Dehydrocorticosterone in the presence of carbenoxolone is a more potent sodium retainer than corticosterone
Steroids 1993 Jan;58(1):24-8.PMID:8430442DOI:10.1016/0039-128x(93)90013-d.
In vivo, corticosterone and 11-Dehydrocorticosterone are interconverted in the liver and possibly kidney by 11 beta-hydroxysteroid dehydrogenase. In an effort to evaluate the relevance of this reversible reaction in relation to urinary sodium and potassium excretion, we investigated the effects of 11-Dehydrocorticosterone in the presence and absence of carbenoxolone, a potent inhibitor of the oxidative component of 11 beta-hydroxysteroid dehydrogenase, and compared them with the effects of similar doses of corticosterone in carbenoxolone-treated rats. All experiments were performed on adrenalectomized male rats. Here we describe that in carbenoxolone-treated rats 11-Dehydrocorticosterone and corticosterone display antinatriuretic activity, although under the conditions of this study 11-Dehydrocorticosterone is a more potent sodium retainer than its parent steroid corticosterone. In addition, the antinatriuretic effects of 11-Dehydrocorticosterone (like the antinatriuretic effects of corticosterone in carbenoxolone-treated rats) were blocked by the specific antimineralocorticoid RU28318.
Quantitative analysis of 11-Dehydrocorticosterone and corticosterone for preclinical studies by liquid chromatography/triple quadrupole mass spectrometry
Rapid Commun Mass Spectrom 2020 Sep;34 Suppl 4(Suppl 4):e8610.PMID:31677354DOI:10.1002/rcm.8610.
Rationale: The activity of the glucocorticoid activating enzyme 11β-hydroxysteroid dehydrogenase type-1 (11βHSD1) is altered in diseases such as obesity, inflammation and psychiatric disorders. In rodents 11βHSD1 converts inert 11-Dehydrocorticosterone (11-DHC) into the active form, corticosterone (CORT). A sensitive, specific liquid chromatography/tandem mass spectrometry method was sought to simultaneously quantify total 11-DHC and total and free CORT in murine plasma for simple assessment of 11βHSD1 activity in murine models. Methods: Mass spectrometry parameters were optimised and a method for the chromatographic separation of CORT and 11-DHC was developed. Murine plasma was prepared by 10:1 chloroform liquid-liquid extraction (LLE) for analysis. Limits of quantitation (LOQs), linearity and other method criteria were assessed, according to bioanalytical method validation guidelines. Results: Reliable separation of 11-DHC and CORT was achieved using an ACE Excel 2 C18-AR (2.1 × 150 mm; 2 μm) fused core column at 25°C, with an acidified water/acetonitrile gradient over 10 min. Analytes were detected by multiple reaction monitoring after positive electrospray ionisation (m/z 345.1.1 ➔ 121.2, m/z 347.1 ➔ 121.1 for 11-DHC and CORT, respectively). The LOQs were 0.25 and 0.20 ng/mL for 11-DHC and CORT, respectively. Conclusions: This LC/MS method is suitable for the reliable analysis of 11-DHC and CORT following simple LLE of murine plasma, bringing preclinical analysis in line with recommendations for clinical endocrinology and biochemistry.
11 beta-Hydroxysteroid dehydrogenase
Vitam Horm 1999;57:249-324.PMID:10232052doi
In mammalian tissues, at least two isozymes of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyze the interconversion of hormonally active C11-hydroxylated corticosteroids (cortisol, corticosterone) and their inactive C11-keto metabolites (cortisone, 11-Dehydrocorticosterone). The type 1 and type 2 11 beta-HSD isozymes share only 14% homology and are separate gene products with different physiological roles, regulation, and tissue distribution. 11 beta-HSD2 is a high affinity NAD-dependent dehydrogenase that protects the mineralocorticoid receptor from glucocorticoid excess; mutations in the HSD11B2 gene explain an inherited form of hypertension, the syndrome of apparent mineralocorticoid excess in which cortisol acts as a potent mineralocorticoid. By contrast, 11 beta-HSD1 acts predominantly as a reductase in vivo, facilitating glucocorticoid hormone action in key target tissues such as liver and adipose tissue. Over the 10 years, 11 beta-HSD has progressed from an enzyme merely involved in the peripheral metabolism of cortisol to a crucial pre-receptor signaling pathway in the analysis of corticosteroid hormone action. This review details the enzymology, molecular biology, distribution, regulation, and function of the 11 beta-HSD isozymes and highlights the clinical consequences of altered enzyme expression.
11-Dehydrocorticosterone causes metabolic syndrome, which is prevented when 11β-HSD1 is knocked out in livers of male mice
Endocrinology 2013 Oct;154(10):3599-609.PMID:23832962DOI:10.1210/en.2013-1362.
Metabolic syndrome is growing in importance with the rising levels of obesity, type 2 diabetes, and insulin resistance. Metabolic syndrome shares many characteristics with Cushing's syndrome, which has led to investigation of the link between excess glucocorticoids and metabolic syndrome. Indeed, increased glucocorticoids from intracellular regeneration by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) drives insulin resistance and increases adiposity, but these metabolic changes are assumed to be due to increased circulating glucocorticoids. We hypothesized that increasing the substrate for 11β-HSD1 (11-Dehydrocorticosterone, 11-DHC) would adversely affect metabolic parameters. We found that chronic administration of 11-DHC to male C57BL/6J mice resulted in increased circulating glucocorticoids, and down-regulation of the hypothalamic-pituitary-adrenal axis. This elevated 11β-HSD1-derived corticosterone led to increased body weight gain and adiposity and produced marked insulin resistance. Surprisingly liver-specific 11β-HSD1 knockout (LKO) mice given 11-DHC did not show any of the adverse metabolic effects seen in wild-type mice. This occurred despite the 11-DHC administration resulting in elevated circulating corticosterone, presumably from adipose tissue. Mice with global deletion of 11β-HSD1 (global knockout) were unaffected by treatment with 11-DHC, having no increase in circulating corticosterone and exhibiting no signs of metabolic impairment. Taken together, these data show that in the absence of 11β-HSD1 in the liver, mice are protected from the metabolic effects of 11-DHC administration, even though circulating glucocorticoids are increased. This implies that liver-derived intratissue glucocorticoids, rather than circulating glucocorticoids, contribute significantly to the development of metabolic syndrome and suggest that local action within hepatic tissue mediates these effects.