Disease relevance of Cortexolone

• A partial adrenal insufficiency was found during Synacthen stimulation, confirmed by a slight increase of 11-desoxycortisol after metyrapone, despite a sufficient rise in ACTH levels [1].
• To determine whether the inhibitory protein was induced through glucocorticoid or mineralocorticoid receptor occupancy, cultured Morris minimal deviation hepatoma cells were pre-treated with the antiglucocorticoid cortexolone or the mineralocorticoid receptor antagonist spironolactone [2].
• At the same time, serum 11-desoxycortisol levels increased in all patients, while plasma ACTH increased in patients with pituitary Cushing's disease and the ectopic ACTH-syndrome [3].
• Toxicity experiments indicate that of the solvents examined octane is the least toxic to the Curvularia lunata substance S biotransformation system under consideration [4].
• In hyperplasia, the changes in 11-desoxycortisol and 17-OH-P (respectively by CPB assay and RIA after LH-20-Sephadex separation) were the reverse of those for cortisol 2 h and 24 h after metyrapone administration [5].

High impact information on Cortexolone

• Addition of cortisol (10(-6) to 10(-8) M) and related glucocorticoid congeners to cultures of rat parathyroid glands stimulated dose-related increases in parathyroid hormone secretion; the addition of deoxycorticosterone or cortexolone was without effect [6].
• Cortexolone has no effect, however, on the induction of (2'-5')A polymerase by interferon [7].
• The acute stimulation by dexamethasone was antagonized by prior addition of progesterone or cortexolone to the hepatocyte suspensions [8].
• The dissociation constants determined for cortisol, cortisone, cortexolone, progesterone, and 20beta-hydroxyprogesterone were at least 1 order of magnitude greater than the corresponding kinetic constants, and these findings suggest the presence of a kinetically insignificant binding site [9].
• At 125 days gestation, there was a significant increase in fetal plasma ACTH and 11-desoxycortisol by 24 h after (+24 h) the start of the metyrapone infusion, and plasma cortisol concentrations were not different at +24 h when compared with pre-infusion values [10].

Biological context of Cortexolone

• This inhibition of programmed cell death of the palatal midline epithelium by each drug is virtually completely blocked by the antiglucocorticoid, cortexolone, whose blocking action results from competitive binding of the glucocorticoid receptor site [11].
• Novel reduction and hydroxylation products formed by Aspergillus fumigatus from Reichstein's substance S [12].
• The 11-beta hydroxylation of the steroid precursor Reichstein's substance S (cortexolone) to hydrocortisone by Curvularia lunata cells is used as a model system for investigating the basis of the effect of solvent choice on multiphase biotransformation reaction kinetics [4].
• Some nutritional requirements of a mixed culture transforming Reichstein's compound S into prednisolone [13].
• The induction of NO synthesis was inhibited in a concentration-dependent manner by the glucocorticoids dexamethasone (IC50 = 5 nM) and hydrocortisone (IC50 = 20 nM) and this effect was partially antagonized by progesterone and cortexolone [14].

Anatomical context of Cortexolone

• Cortexolone, but not prednisolone, initiated the appearance of several protein bands of different molecular weights in the migrating conjunctival epithelium, while treatment with prednisolone plus cortexolone resulted in a pattern of protein bands which resembled the saline-treated control [15].
• Application of either prednisolone or cortexolone to corneal epithelium resulted in similar protein synthesis patterns, each showing two new protein bands of about 15K and 32K [15].
• No effect on transcription is observed if the liver or thymus cytosol is heat activated in the presence of the glucocorticoid antagonist, cortexolone [16].
• Progesterone, estradiol, testosterone, cortisol, and 11-desoxycortisol (compound S) were added to cultures of human lymphocytes stimulated with phytohaemagglutinin (PHA) and purified protein derivative (PPD) [17].
• The immobilized cells have been used to catalyze the continuous delta1-dehydrogenation of Reichstein's substance S under various conditions in the presence of phenazine methosulfate (PMS), an electron acceptor for the cell-free delta1-dehydrogenase [18].

Associations of Cortexolone with other chemical compounds

• In vitro antiglucocorticoids (cortexolone and progesterone) were evaluated as in vivo antagonists of dexamethasone-induced increases in liver tyrosine amino transferase (TAT; EC 2.6.1.5), tryptophan oxygenase (TPO; EC 1.13.1.12), and glycogen deposition [19].
• Monolayer cultures of C-1300 murine neuroblastoma (clone NBP2) were treated with the following compounds in ethanol: dexamethasone, triamcinolone acetonide, hydrocortisone, cortexolone, androstenedione, testosterone, estradiol-17 beta; or with the phosphodiesterase inhibitor Ro20-1724 [4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone] [20].
• Peak cortisol levels after Synacthen also correlated with the sum of cortisol and 11-desoxycortisol values after metyrapone, indicating the presence of a maximum adrenal response and a sufficient rise of endogenous ACTH after metyrapone [1].
• Cytochrome P-450 content significantly increased after the culture supplementation by the second substrate, phenanthrene or cortexolone, adequately [21].
• A first assay based on stable isotope dilution/gas chromatography-mass spectrometry (ID/GC-MS) has been developed for plasma 11-deoxycortisol (Reichstein's compound S), the leading hormonal marker of 11beta-hydroxylase deficiency [22].

Gene context of Cortexolone

• We now report on 11-desoxycortisol (11-desoxy-F) and 2 alpha-methylcortisone, substances which possess no intrinsic antinatriuretic activity, are not metabolized by 11 beta-OHSD and yet cause Na+ retention in CBX-treated ADX rats [23].
• Metyrapone failed to increase ACTH and 11-desoxycortisol [24].
• Cortisol, prednisolone and Reichstein substance S (11-deoxy-17-hydroxycorticosterone) were all effective in stimulating PNMT mRNA expression while cortisone, progesterone and beta-estradiol were without effect [25].
• A new antagonist, 6 beta-bromoprogesterone, was found to be nontoxic and was more potent than cortexolone in blocking the TPO and glycogen responses [19].
• This DEX-induced increase in FN expression was progressive after the first 7 d of treatment and was blocked partially with a glucocorticoid antagonist, cortexolone [26].

Analytical, diagnostic and therapeutic context of Cortexolone

• Although baseline 11-desoxycortisol (S) and the plasma S/ACTH ratio were unaltered, the delta max S/F ratio increased after treatment (P less than 0.01), suggesting an inhibition of 11 beta-hydroxylase activity [27].
• The localization in the mouse brain of corticosterone, the natural glucocorticoid in the mouse, and cortexolone, reported to be a glucocorticoid antagonist, was studied by autoradiography 30 min after in vivo administration of the tritiated compounds [28].
• A novel rapid color development assay and thin layer chromatography were used to qualitatively establish the ability of the fungi to convert cortexolone to hydrocortisone [29].

References