Quantitative Profiling of Cortisol Metabolites in Human Urine by High-Resolution Accurate-Mass Ms

Wang, Yi; Fujioka, Naomi; Xing, Chengguo

doi:10.4155/bio-2018-0182

Cited by 17 publications

(12 citation statements)

References 38 publications

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“…Given the absence of PRH-evoked decreases in UGT2B7 expression in SCHH, the observed reduction of labetalol Gluc-2 formation following PRH CKTL treatment was not mediated by suppression of UGT2B7 protein expression. It is well-established that E2, E3, E4, and CRT undergo glucuronidation, and that rates of UGT2B7-mediated glucuronidation of E2 and E3 are very high (Gall et al, 1999;Visser et al, 2008;Wang et al, 2018). Moreover, while P4 does not directly undergo glucuronidation, the P4 metabolites pregnanediol and pregnanetriol are metabolized to their respective glucuronides (Meng et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-Related Hormones Increase UGT1A1-Mediated Labetalol Metabolism in Human Hepatocytes

et al. 2021

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Pregnancy-related hormones (PRH) are recognized as important regulators of hepatic cytochrome P450 enzyme expression and function. However, the impact of PRH on the hepatic expression and function of uridine diphosphate glucuronosyltransferases (UGTs) remains unclear. Using primary human hepatocytes, we evaluated the effect of PRH exposure on mRNA levels and protein concentrations of UGT1A1, UGT2B7, and other key UGT enzymes, and on the metabolism of labetalol (a UGT1A1 and UGT2B7 substrate commonly prescribed to treat hypertensive disorders of pregnancy). Sandwich-cultured human hepatocytes (SCHH) from female donors were exposed to the PRH estradiol, estriol, estetrol, progesterone, and cortisol individually or in combination. We quantified protein concentrations of UGT1A1, UGT2B7, and four additional UGT1A isoforms in SCHH membrane fractions and evaluated the metabolism of labetalol to its glucuronide metabolites in SCHH. PRH exposure increased mRNA levels and protein concentrations of UGT1A1 and UGT1A4 in SCHH. PRH exposure also significantly increased labetalol metabolism to its UGT1A1-derived glucuronide metabolite in a concentration-dependent manner, which positively correlated with PRH-induced changes in UGT1A1 protein concentrations. In contrast, PRH did not alter UGT2B7 mRNA levels or protein concentrations in SCHH, and formation of the UGT2B7-derived labetalol glucuronide metabolite was decreased following PRH exposure. Our findings demonstrate that PRH alter expression and function of UGT proteins in an isoform-specific manner and increase UGT1A1-mediated labetalol metabolism in human hepatocytes by inducing UGT1A1 protein concentrations. These results provide mechanistic insight into the increases in labetalol clearance observed in pregnant individuals.

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Section: Discussionmentioning

confidence: 99%

Pregnancy-Related Hormones Increase UGT1A1-Mediated Labetalol Metabolism in Human Hepatocytes

et al. 2021

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“…Cortisol metabolites were found to be a better indicator than urinary cortisol in the setting of cyclical Cushing syndrome and in patients with adrenal incidentalomas [31] . It has also been suggested that measures of the major metabolites of cortisol may be better surrogates for total cortisol secretion than measures of cortisol alone [32] . While urinary free cortisol is indicative of cortisol’s metabolic activity, with a significant amount of cortisol being bound to either cortisol-binding globulin or albumin, the cortisol metabolites are more indicative of total cortisol production.…”

Section: Discussionmentioning

confidence: 99%

Dried urine and salivary profiling for complete assessment of cortisol and cortisol metabolites

Newman¹,

Curran²,

Mayfield

2020

Journal of Clinical & Translational Endocrinology

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Highlights Dried urine is an alternative to liquid urine for measuring cortisol and its metabolites. 4-spot urine sampling is representative of a 24-hour urine collection. 4-spot urinary cortisol measures reflect the diurnal pattern of change in cortisol. Comprehensive profiling of cortisol is viable using both saliva plus dried urine samples.

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“…Calibration curves, limit of detection (LOD) and limit of quantification (LOQ) of kavalactones, 3-mA, cortisol, and cortisol metabolites have been established as described previously (15,30,33). Performance of these methods were validated by specificity, precision, accuracy, within-day, and betweenday reproducibility using the pure standards added into the blank matrix at three to four different concentrations on three different days.…”

Section: Methods Validationmentioning

confidence: 99%

“…Urinary TCE was measured as described previously (33). Plasma cortisol was quantified following the same procedures with slight modifications.…”

Section: Measurement Of Urinary Tce and Plasma Cortisolmentioning

confidence: 99%

“…3B, 15 of 21 participants had reduction in plasma cortisol after kava use (ratio of geometric means ¼ 0.66; 95% CI, 0.51-0.86; P ¼ 0.004). We also quantified the sum of the major metabolites of cortisol in the urine samples (termed total cortisol equivalent, TCE) following our recently reported methods (33). Kava use resulted in a 59.0% reduction in urinary TCE in the 0 to 6 hours samples (Fig.…”

Section: Effect Of Kava On Urinary Tne Mceq Plasma Cortisol and Urinamentioning

confidence: 99%

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The Impact of One-week Dietary Supplementation with Kava on Biomarkers of Tobacco Use and Nitrosamine-based Carcinogenesis Risk among Active Smokers

Wang

Narayanapillai

Tessier

et al. 2020

Cancer Prevention Research

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Tobacco smoking is the primary risk factor for lung cancer, driven by the addictive nature of nicotine and the indisputable carcinogenicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as well as other compounds. The integration of lung cancer chemoprevention with smoking cessation is one potential approach to reduce this risk and mitigate lung cancer mortality. Experimental data from our group suggest that kava, commonly consumed in the South Pacific Islands as a beverage to promote relaxation, may reduce lung cancer risk by enhancing NNK detoxification and reducing NNK-derived DNA damage. Building upon these observations, we conducted a pilot clinical trial to evaluate the effects of a 7-day course of kava on NNK metabolism in active smokers. The primary objective was to compare urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL plus its glucuronides, major metabolites of NNK) before and after kava administration as an indicator of NNK detoxification. Secondary objectives included determining kava's safety, its effects on DNA damage, tobacco use, and cortisol (a biomarker of stress). Kava increased urinary excretion of total NNAL and reduced urinary 3-methyladenine in participants, suggestive of its ability to reduce the carcinogenicity of NNK. Kava also reduced urinary total nicotine equivalents, indicative of its potential to facilitate tobacco cessation. Plasma cortisol and urinary total cortisol equivalents were reduced upon kava use, which may contribute to reductions in tobacco use. These results demonstrate the potential of kava intake to reduce lung cancer risk among smokers.

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Quantitative Profiling of Cortisol Metabolites in Human Urine by High-Resolution Accurate-Mass Ms

Cited by 17 publications

References 38 publications

Pregnancy-Related Hormones Increase UGT1A1-Mediated Labetalol Metabolism in Human Hepatocytes

Pregnancy-Related Hormones Increase UGT1A1-Mediated Labetalol Metabolism in Human Hepatocytes

Dried urine and salivary profiling for complete assessment of cortisol and cortisol metabolites

The Impact of One-week Dietary Supplementation with Kava on Biomarkers of Tobacco Use and Nitrosamine-based Carcinogenesis Risk among Active Smokers

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