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Inflammation
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Among these steroids a metabolite, etiocholanolone, has been shown to induce fever in human subjects.248,258,519 Etiocholanolone is derived from either testosterone, Δ4-androstene- 3,17,-dione or dehydroepiandrosterone (Figure 22), and it probably originates from the testes and adrenal cortex. Etiocholanolone has no hormonal activity; it is excreted into the urine in free form and conjugated with glucuronic acid. Etiocholanolone is pyrogenic to humans only in its unconjugated form and in amounts that are known to be produced under physiological circumstances. Androsterone, which is formed in parallel with etiocholanolone, is only slightly pyrogenic. This steroid contains the allo ring structure.
Fever In Endocrinologic Disorders
Published in Benedict Isaac, Serge Kernbaum, Michael Burke, Unexplained Fever, 2019
Ygal Gilboa, Elisabeth Horer, B. Isaac
It has been found that some steroids, like Cortisol and estradiol, are antipyrogenic while etiocholanolone, a known metabolite of the androgens, is a potent pyrogen in man.42,43 Bondy44 and Kappas45 described the pyrogenic effect of etiocholanolone as well as increased levels of this steroid in some cases of congenital adrenal hyperplasia associated with fever. The problem of the connection of etiocholanolone with different types of prolonged or periodic fevers has had its ups and downs. In most of the cases in which etiocholanolone was estimated, no increase was found. However, occasionally cases of fever and increased etiocholanolone levels have been described, one as recent as 1981.46 In the opinion of most authors etiocholanolone is no more considered in the differential diagnosis of obscure fever.47
Steroid Δ4-Reductases: their Physiological Role and Significance
Published in Ronald Hobkirk, Steroid Biochemistry, 1979
As will be detailed, many androgen target tissues have the capacity to convert testosterone to 5α-dihydrotestosterone. This metabolite, which in some bioassays is more potent than testosterone itself, is probably the important intracellular andogen in these target tissues. The presence of the target tissue Δ4-5α-reductases accounts for a higher urine androsterone/etiocholanolone ratio (for the 14C metabolites of 14C-testosterone or for endogenous precursors) for men than for women.95 Approximately 40% of a dose of intravenously administered 14C-testosterone is converted to urine androsterone and etiocholanolone.95 The mean 14C-androsterone/14C-etiocholanolone ratios were 1.5 and 0.9 for young men and women, respectively, and 1.0 and 0.4 for old men and women respectively. The ratios were significantly different for both age groups. In support of the male androgen target tissues playing a significant role in the production of the 5α-metabolite androsterone was the finding that the ratios were not significantly different for boys and girls (1.7 and 1.9, respectively). There was no sex difference for the 5α/5β androstanediols for any of the age groups. That the sex hormone binding globulin influences the entry of testosterone into target tissues where Δ4-5α-reduction occurs is supported by the finding of less 5α-metabolites in situations where the level of the binding protein has been increased by estrogen administration.96
Effects of night shift on the cognitive load of physicians and urinary steroid hormone profiles – a randomized crossover trial
Published in Chronobiology International, 2018
Wolf Osterode, Sandra Schranz, Galateja Jordakieva
Concerning our second aim of the study namely to investigate changes of steroid hormones after 24 h on duty (Table 3), mostly no significant dynamics were found. Only pregnanetriol and the ratio of androsterone/etiochoanolone were found to be reduced after 24 h on duty. Pregnanetriol is a urinary metabolite of 17-alpha-hydroxyprogesterone and a precursor in the biosynthesis of cortisol. While Vierhapper and Nowotny found an enormous enhanced excretion of glucocorticoids and main androgen metabolites after a night shift by male residents, Singer and Zumoff reported a suppression of these steroids, which would support the fact that stress and sleep deprivation suppress gonadal steroids. We may assume that stress and sleep deprivation were not extensive enough in our collective to exhibit clear steroid dynamics, which on the other hand justifies the reduction of longer time on duty and reduced responsibility for more medical departments in former times. The excretion ratio of androsterone/etiocholanolone indeed showed significant alterations implicating disturbances of an androgen metabolism. The change in the ratio of androsterone to etiocholanolone in favor of the latter implies hypothalamus involvement in androgen metabolism dynamics (Johnsen 1968).
FXR modulators for enterohepatic and metabolic diseases
Published in Expert Opinion on Therapeutic Patents, 2018
Hong Wang, Qingxian He, Guangji Wang, Xiaowei Xu, Haiping Hao
Apart from BAs and relative derivatives, several other steroidal compounds, including 5α-androstan-3α-ol-17-one (androsterone), 5β-androstan-3α-ol-17-one (etiocholanolone) and MFA-1 [17-(4-hydroxybenzoyl) androsta-3,5-diene-3-carboxylic acid] [57,58], have been demonstrated as FXR agonists.
Novel insights into the pharmacometabonomics of first-line tuberculosis drugs relating to metabolism, mechanism of action and drug-resistance
Published in Drug Metabolism Reviews, 2018
As mentioned earlier, RIF activates PXR, a member of the nuclear receptor superfamily of ligand-dependent transcription factors. The activated PXR in turn binds to the response elements in the promotors and upregulates the transcription of specific transporters and drug metabolizing enzymes, including that of the CYPs (Ramappa and Aithal 2013), with as much as 7.7-fold (Rae et al. 2001). With the aim of identifying changes to the endogenous metabolite concentrations associated with RIF-induced PXR activation, Cho et al. (2009) compared the urinary metabolite profiles of pxr-humanized mice receiving a RIF-containing diet (10 mg/kg/d) to those receiving a control diet, using a UPLC-TOFMS metabolomics approach. Results indicated significantly reduced levels of two urinary vitamin E (tocopherol) metabolites; α-carboxyethyl hydroxychroman (CEHC) glucuronide and γ-CEHC β-D-glucoside (Table 2), which is presumably an outcome of a PXR-mediated repression of hepatic sterol carrier protein 2 (which is involved in peroxisomal β-oxidation of branched-chain fatty acids) (Figure 2), since these metabolite variations were not detected when using pxr-null mice. For the same purpose, Kim et al. (2013) applied global metabolic profiling (via UPLC/QTOF-MS analyses) and semi-targeted steroid profiling (via GC-MS analyses) of urine samples collected from 12 healthy human male subjects before and after RIF ingestion. The aforementioned global metabolomics analyses of the two groups indicated significantly increased levels of glycochenodeoxycholate sulfate and hydroxytestosterone sulfate, accompanied by vastly reduced levels of dehydroepiandrosterone (DHEA) sulfate, androsterone sulfate, and p-cresol, after RIF ingestion. The semi-targeted urinary steroid analyses revealed elevated concentrations of 16α-OH-A-dione, 16α-OH-DHEA, 7α-DHEA, 7β-DHEA and 11β-OH-A-dione and reduced levels of DHEA, androsterone, etiocholanolone, estrone, β-cortolone, and allo-tetrahydrocortisone in the RIF group (Table 2). These results suggest that the RIF-induced PXR-activation inhibits CYP17A/19A and activates CYP1A/3A/7B/11B/2C. It was furthermore suggested that these metabolite markers and their ratios could potentially be used for predicting the extent of PXR activation, to monitor the activities of various drug-metabolizing enzymes and/or to predict drug-drug interactions (Kim et al. 2013).