18-Oxocortisol
目录号 : GC62759
18-Oxocortisol 是由醛固酮合酶 (CYP11B2) 产生的皮质醇衍生物。18-Oxocortisol 是天然存在的盐皮质激素 (mineralocorticoid) 激动剂。18-Oxocortisol 是肾上腺静脉采样中的生物标志物。
Cas No.:2410-60-8
Sample solution is provided at 25 µL, 10mM.
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18-Oxocortisol is a derivative of cortisol that is produced by aldosterone synthase (CYP11B2). 18-Oxocortisol is a naturally occurring mineralocorticoid agonist. 18-Oxocortisol is a biomarker in adrenal vein sampling[1][2][3].
Administration of 18-oxocortisol to rats induces a mineralocorticoid-type hypertension with hypokalemia, cardiac and renal enlargement and cardiovascular lesions. Administration of 18-oxocortisol to sheep also causes a rapid increase in blood pressure. However, the doses required for increasing blood pressure are high[3].
[1]. Nakamura Y, et al. 18-oxocortisol measurement in adrenal vein sampling as a biomarker for subclassifying primaryaldosteronism. J Clin Endocrinol Metab. 2011 Aug;96(8):E1272-8.
[2]. Ulick S, et al. 18-oxocortisol, a naturally occurring mineralocorticoid agonist. Endocrinology. 1983 Dec;113(6):2320-2.
| Cas No. | 2410-60-8 | SDF | |
| 分子式 | C21H28O6 | 分子量 | 376.44 |
| 溶解度 | 储存条件 | Store at -20°C | |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6565 mL | 13.2823 mL | 26.5647 mL |
| 5 mM | 0.5313 mL | 2.6565 mL | 5.3129 mL |
| 10 mM | 0.2656 mL | 1.3282 mL | 2.6565 mL |
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18-Oxocortisol: A journey
J Steroid Biochem Mol Biol 2023 Mar 13;230:106291.PMID:36921907DOI:10.1016/j.jsbmb.2023.106291.
The search for mineralocorticoids to explain some cases of low renin hypertension with suppressed aldosterone levels led to the isolation of the abundant steroid 18-hydroxycortisol in human urine. 18-Hydroxycortisol proved to be inactive, but because of its similarity to precursors for the synthesis of aldosterone, bullfrog adrenals were incubated with cortisol, resulting in the discovery of 18-Oxocortisol which is structurally similar to aldosterone, but with a 17α-hydroxy group like cortisol. 18-Oxocortisol is a weak mineralocorticoid. Its synthesis occurs primarily in the zona glomerulosa where co-expression of the CYP11B2 (aldosterone synthase) and the CYP17A1 (17α-hydroxylase) occurs in a variable number of cells. The clinical value of the measurement of 18-Oxocortisol is that it serves to distinguish subtypes of primary aldosteronism. It is significantly elevated in patients with aldosterone-producing adenomas in comparison to those with idiopathic bilateral hyperaldosteronism and helps predict the type of somatic mutation in the aldosterone-producing adenomas, as it is higher in those with KCNJ5 mutations compared to other gene mutations.
Origin of circulating 18-Oxocortisol in the normal human adrenal
Mol Cell Endocrinol 2022 Sep 15;555:111720.PMID:35870737DOI:10.1016/j.mce.2022.111720.
18-Oxocortisol is the product of the metabolism of 11-deoxycortisol by the mitochondrial enzyme aldosterone synthase (CYP11B2). The traditional concept is that the CYP11B2 is exclusively expressed in zona glomerulosa cells and the 17α-hydroxylase (CYP17A1) enzyme, required to synthesize 11-deoxycortisol, is in the zona fasciculata of the human adrenal. It has been postulated that the substrate for 18-Oxocortisol is either cortisol from the circulation or from zona fasciculata cells adjacent to the zona glomerulosa. P-glycoprotein, which is highly expressed in steroidogenic cells of the adrenal gland, efficiently expels cortisol from the cell. Double immunofluorescence staining for the CYP11B2 and CYP17A1 enzymes in 7 human adrenals demonstrated that a highly variable number of cells in different areas of the zona glomerulosa co-expressed both enzymes. In addition, there were a variable number of cells that exclusively expressed the CYP17A1 embedded within the zona glomerulosa surrounded by CYP11B2-expressing cells. 18-Oxocortisol in the media of human adrenocortical HAC15 cells was measured by ELISA after incubation with and without 10 nM of angiotensin II to stimulate CYP11B2 activity, with and without the 3β-hydroxysteroid dehydrogenase (HSD3B) inhibitor trilostane, and with variable amounts of cortisol or 11-deoxycortisol. Cortisol was a poor substrate, while 11-deoxycortisol was a significant substrate for the synthesis of 18-Oxocortisol. These data suggest that the biosynthesis of 18-Oxocortisol in the human adrenal is likely catalyzed by co-expression of the two crucial enzymes CYP17A1 and CYP11B2 in a small proportion of cells within the zona glomerulosa. It is also possible that 11-deoxycortisol diffusing from cells expressing only CYP17A1 interspersed with cells expressing the CYP11B2 enzyme may be a paracrine substrate in the synthesis of 18-Oxocortisol.
DIAGNOSIS OF ENDOCRINE DISEASE: 18-Oxocortisol and 18-hydroxycortisol: is there clinical utility of these steroids?
Eur J Endocrinol 2018 Jan;178(1):R1-R9.PMID:28904009DOI:10.1530/EJE-17-0563.
Since the early 1980s 18-hydroxycortisol and 18-Oxocortisol have attracted attention when it was shown that the urinary excretion of these hybrid steroids was increased in primary aldosteronism. The development and more widespread use of specific assays has improved the understanding of their role in the (patho)physiology of adrenal disorders. The adrenal site of synthesis is not fully understood although it is clear that for the synthesis of 18-hydroxycortisol and 18-Oxocortisol the action of both aldosterone synthase (zona glomerulosa) and 17α-hydroxylase (zona fasciculata) is required with cortisol as main substrate. The major physiological regulator is ACTH and the biological activity of both steroids is very low and therefore only very high concentrations might be effective in vivo In healthy subjects, the secretion of both steroids is low with 18-hydroxycortisol being substantially higher than that of 18-Oxocortisol. The highest secretion of both steroids has been found in familial hyperaldosteronism type 1 (glucocorticoid-remediable aldosteronism) and in familial hyperaldosteronism type 3. Lower but yet substantially increased secretion is found in patients with aldosterone-producing adenomas in contrast to bilateral hyperplasia in whom the levels are similar to patients with hypertension. Several studies have attempted to show that these steroids, in particular, peripheral venous plasma 18-Oxocortisol, might be a useful discriminatory biomarker for subtyping PA patients. The current available limited evidence precludes the use of these steroids for subtyping. We review the biosynthesis, regulation and function of 18-hydroxycortisol and 18-Oxocortisol and their potential utility for the diagnosis and differential diagnosis of patients with primary aldosteronism.
Aldosterone and 18-Oxocortisol Coaccumulation in Aldosterone-Producing Lesions
Hypertension 2018 Dec;72(6):1345-1354.PMID:30571232DOI:10.1161/HYPERTENSIONAHA.118.11243.
Primary aldosteronism is a secondary hypertensive disease caused by autonomous aldosterone production that often caused by an aldosterone-producing adenoma (APA). Immunohistochemistry of aldosterone synthase (CYP11B2) shows the presence of aldosterone-producing cell clusters (APCCs) even in non-primary aldosteronism adult adrenal cortex. An APCC-like structure also exists as possible APCC-to-APA transitional lesions (a speculative designation) in primary aldosteronism adrenals. However, whether APCCs produce aldosterone or 18-Oxocortisol, a potential serum marker of APA, remains unknown because of lack of technology to visualize adrenocorticosteroids on tissue sections. To address this obstacle, in this study, we used highly sensitive Fourier transform ion cyclotron resonance mass spectrometry to image various adrenocorticosteroids, including 18-Oxocortisol, in adrenal tissue sections from 8 primary aldosteronism patients with APCC (cases 1-4), possible APCC-to-APA transitional lesions (case 5), and APA (cases 6-8). Further analyses by tandem mass spectrometry imaging allowed us to differentially visualize aldosterone from cortisone, which share identical mass-to-charge ratio value ( m/z). In conclusion, these advanced imaging techniques revealed that aldosterone and 18-Oxocortisol coaccumulated within CYP11B2-expressing lesions. These imaging outcomes along with a growing body of aldosterone research led us to build a progressive development hypothesis of an aldosterone-producing pathology in the adrenal glands.
Regulation of 18-Oxocortisol and 18-hydroxycortisol by the renin-angiotensin system and ACTH in man
J Steroid Biochem Mol Biol 1993 Sep;46(3):395-9.PMID:9831489DOI:10.1016/0960-0760(93)90230-t.
Based on urinary excretion studies the secretion of the cortisol derivatives, 18-Oxocortisol and 18-hydroxycortisol are believed to be regulated by ACTH and to a lesser degree by the renin-angiotensin system. Plasma concentrations of 18-Oxocortisol and 18-hydroxycortisol were measured during the simultaneous activation of the renin-angiotensin system and inhibition of ACTH secretion. Five healthy male subjects consuming a sodium diet ad libitum were studied. Blood was drawn at 0800 h after 1 h in the supine position. In the first set of experiments, the subjects remained in the supine position from 0800 to 1000 h with or without the oral administration of 2 mg dexamethasone at 0800 h. In the second set of experiments the subjects were placed in the upright position after drawing the 0800 h sample. The subjects were studied with and without dexamethasone administered at 0800 h. Blood was drawn again at 1000 h. Plasma levels of 18-Oxocortisol, 18-hydroxycortisol, ACTH, plasma renin activity (PRA), cortisol, aldosterone and 18-hydroxycorticosterone were measured by radioimmunoassay. None of these parameters changed during the 2 h in the supine position. 18-Oxocortisol, 18-hydroxycortisol, aldosterone, 18-hydroxycorticosterone and PRA increased, but ACTH and cortisol did not change when the subjects were placed in the upright position. After dexamethasone administration, 18-Oxocortisol, 18-hydroxycortisol, cortisol, aldosterone and 18-hydroxycorticosterone decreased in the supine position and no increase occurred in 18-Oxocortisol, 18-hydroxycortisol and 18-hydroxycorticosterone in the upright position. PRA and aldosterone increased and ACTH and cortisol decreased in these subjects. 18-Oxocortisol and 18-hydroxycortisol were more dependent on ACTH regulation and less on the renin-angiotensin system than aldosterone.