Disease relevance of Cortexolone

• Subnormal plasma 11-deoxycortisol (compound S) responses to metyrapone were found in patients with adrenal insufficiency or with Cushing syndrome caused by adrenal tumors and in those receiving long-term glucocorticoid or diphenylhydantoin sodium therapy [1].
• Analysis of the substrate/product ratios 11-deoxycortisol/cortisol and deoxycorticosterone/corticosterone revealed defective 11 beta-hydroxylation in women with hirsutism [2].
• Serum 21-Deoxycortisol, 17-Hydroxyprogesterone, and 11-deoxycortisol in classic congenital adrenal hyperplasia: clinical and hormonal correlations and identification of patients with 11beta-hydroxylase deficiency among a large group with alleged 21-hydroxylase deficiency [3].
• Elevated plasma concentrations of estrone, androstenedione, and 11-deoxycortisol provide useful markers for adrenal tumors, but no one steroid can be relied upon in all tumors, and metastases may lack the steroidogenic capabilities of the primary tumor [4].
• Metabolic processes involving side-chain and ring cleavage of progesterone, 17-hydroxyprogesterone, 11-deoxycortisol and 16-dehydropregnenolone by Arthrobacter simplex were studied [5].

Psychiatry related information on Cortexolone

• No significant difference in the ACTH response to cortisol infusion following metyrapone was observed; however 11-deoxycortisol was significantly decreased in PTSD subjects [6].
• The measurement of post-dexamethasone 11-deoxycortisol and the ratio did not differentiate between endogenous and reactive depression [7].

High impact information on Cortexolone

• After administration of metyrapone, stimulation of 17-OHS excretion greater than 70% or of a plasma 11-deoxycortisol level greater than 400-fold did not result in the misclassification of any of the patients with surgically confirmed cases of ectopic ACTH secretion [8].
• Whereas P450XIB1 only catalyzes hydroxylation at position 11 beta of 11-deoxycorticosterone and 11-deoxycortisol, P450XIB2 catalyzes the synthesis of aldosterone from deoxycorticosterone, a process that successively requires hydroxylation at positions 11 beta and 18 and oxidation at position 18 [9].
• Expression of these cDNAs in cultured COS-1 cells demonstrated that the CYP11B1 product could only 11 beta-hydroxylate 11-deoxycortisol or deoxycorticosterone, whereas the CYP11B2 product could also 18-hydroxylate cortisol or corticosterone [10].
• Subjects with PTSD had higher raw cortisol and higher normed (baseline-related) ACTH and 11-deoxycortisol values after metyrapone independent of treatment with fludrocortisone or placebo [11].
• Results: Analyzing the mutations in vitro revealed an almost absent or negligible CYP21 activity for the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to deoxycorticosterone [12].

Chemical compound and disease context of Cortexolone

• The ratios of progesterone to 17-hydroxyprogesterone and 17-hydroxyprogesterone to 11-deoxycortisol were higher in the adenoma group (p less than 0.005 and p equals 0.06, respectively) [13].
• It is proposed that a steroid profile measuring cortisol, aldosterone, 11-deoxycortisol, and dehydroepiandrosterone would potentially improve the ability to determine the cause of adrenal insufficiency [14].
• 11-Deoxycortisol, dehydroepiandrosterone, and a two-steroid profile each provided fair discrimination between secondary adrenal insufficiency and normal status [14].
• The ultrastructural characteristics of a benign adrenal adenoma that produces deoxycorticosterone and 11-deoxycortisol were examined by transmission electron microscopy [15].
• OBJECTIVE: The prevalence of steroid secretion abnormalities was studied by evaluating the 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (S) responses to adrenocorticotropic hormone (ACTH) stimulation in 48 patients with 'nonfunctioning' incidentalomas and in 10 patients with 'subclinical' Cushing's syndrome [16].

Biological context of Cortexolone

• AF THS and 11-deoxycortisol concentrations were markedly elevated in pregnancies with affected fetuses (P less than 0.01), but normal in nonaffected ones [17].
• The intermediate phenotype most consistently associated with variation at this locus is that of elevated plasma 11-deoxycortisol (S) [18].
• To investigate the safety of 11-deoxycortisol, the biomicroscopic appearance, intraocular pressure (IOP), corneal endothelial count, and microstructure of the corneal endothelium were examined in the rabbits that received injections of 11-deoxycortisol in the anterior chamber [19].
• Antisera were raised using 11-deoxycortisol -3-carboxymethyloxime-bovine serum albumin as immunogen and showed minimal cross reaction with related steroids [20].
• Other steroids (11-deoxycorticosterone, 11-deoxycortisol and progesterone) which have been implicated in oocyte maturation and/or ovulation in lower vertebrates were not identified at such high concentrations and the differences between the serum of both sexes were not so great [21].

Anatomical context of Cortexolone

• The in vitro effects of 13 indole compounds on the synthesis of glucocorticoids and of adrenal androgens in sheep adrenal glands has been studied from 11-deoxycortisol as a precursor [22].
• Early passage (P1-P3) bovine adrenal cortex cells cultured in serum-free medium responded to ACTH (10(-8)M) with increased 11-deoxycortisol production; this effect was not observed in later passage cells (P7-P15) [23].
• In intact rabbit eyes, most of the injected 11-deoxycortisol had disappeared from the anterior chamber by 12 hours after injection [19].
• The injection of 11-deoxycortisol facilitated the complete removal of the vitreous body from the anterior chamber [19].
• The injection of 11-deoxycortisol had no effect on IOP, corneal endothelial density, or the microstructure of the corneal endothelium [19].

Associations of Cortexolone with other chemical compounds

• In healthy women G alleles at -597 and -174 were associated with statistically significant higher circulating levels of IL-6 and basal cortisol, 11-deoxycortisol, and 17-hydroxyprogesterone and a tendency (P < 0.10) for higher total T concentrations compared with -597A and -174C alleles [24].
• Maternal plasma 11-deoxycortisol and delta 4-androstenedione concentrations, determined sequentially throughout gestation, were variable and did not contribute to prenatal diagnosis [17].
• This probably reflected inhibition of C11-hydroxylase, since basal and ACTH-stimulated levels of 11-deoxycortisol were increased in response to CGS 16949A [25].
• Plasma T, androstenedione, and 11-deoxycortisol responses to metyrapone were excessive in PCOS patients, thus indicating a specific adrenal abnormality [26].
• Using multiple regression analysis, decreased cortisol to ACTH ratio was significantly related to higher IL-6 levels and intubation with etomidate (one single bolus), whereas decreased cortisol to 11-deoxycortisol ratio was significantly related only to intubation with etomidate [27].

Gene context of Cortexolone

• The substrate for CYP11B2 is 11-deoxycorticosterone, that of CYP11B1 is 11-deoxycortisol [28].
• However, the responses of DOC (P = 0.002 and P = 0.001, respectively) and 11-deoxycortisol (P = 0.025 and P = 0.002, respectively) were significantly greater in subjects homozygous for SF-1 T and/or intron conversion than in those homozygous for SF-1 C and/or normal intron [29].
• Thereafter ACTH and AVP were sampled at 10-min intervals, CRF at 20-min intervals, and cortisol and 11-deoxycortisol at hourly intervals until 12:00 h on day 2 [30].
• The decline in delta sleep was significantly associated with the magnitude of increase in both 11-deoxycortisol and ACTH [31].
• In our previous studies we had demonstrated that, in children affected with isolated GH deficiency (IGHD), a short-term recombinant growth hormone (rGH) therapy increases the 11-deoxycortisol (S) secretion and induces an IGF-I responsiveness to the ACTH challenge [32].

Analytical, diagnostic and therapeutic context of Cortexolone

• Plasma 11-deoxycortisol (S) was not measured in that longitudinal study [33].
• We have developed a simple, reliable radioimmunoassay for plasma 11-deoxycortisol [34].
• Polarization fluoroimmunoassay of 11-deoxycortisol in serum and saliva [35].
• Determination of serum cortisol and 11-deoxycortisol by liquid chromatography [36].
• During the first 3 h of immobilization, levels of cortisol, 17-hydroxylated precursors, and 11-deoxycortisol increased markedly from initial levels [37].

References