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1

Debono, Miguel, Robert F. Harrison, Martin J. Whitaker, David Eckland, Wiebke Arlt, Brian G. Keevil, and Richard J. Ross. "Salivary Cortisone Reflects Cortisol Exposure Under Physiological Conditions and After Hydrocortisone." Journal of Clinical Endocrinology & Metabolism 101, no. 4 (April 1, 2016): 1469–77. http://dx.doi.org/10.1210/jc.2015-3694.

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Abstract Context: Measuring serum cortisol to evaluate stress, adrenal disease, and monitor hydrocortisone replacement requires venepuncture. Conversely, salivary measurements are noninvasive. Objective: This study aimed to investigate measurement of salivary cortisol and cortisone as alternatives to serum cortisol. Design and Setting: This was a prospective cross-over study in a clinical research facility. Patients and Methods: Over three periods (Period 1, 24-h physiological cortisol rhythm; Periods 2 and 3, after 20 mg oral and iv hydrocortisone) 14 male volunteers had serum and saliva cortisol and cortisone, serum albumin, cortisol-binding globulin, and free cortisol measured. Data were analyzed for rhythm parameters and correlations. Linear mixed-effects modelling was performed to determine the relationship between serum cortisol and salivary cortisone. Results: Serum cortisol and cortisone showed similar circadian rhythms with large peak:trough ratios (cortisol median ratio, 11). Albumin and cortisol-binding globulin showed minor peak:trough ratios <1.2. When serum cortisol was <74 (SD, 29) nmol/L, salivary cortisol was not detectable but salivary cortisone was always detected. Salivary cortisol post-oral hydrocortisone produced spurious results due to contamination. Under physiological conditions, salivary cortisone correlated strongly with serum cortisol (ρ, 0.91; 95% confidence interval, 0.89–0.93; P < .001). Similarly, following iv or oral hydrocortisone, salivary cortisone correlated strongly with serum cortisol (ρ, 0.91; 95% confidence interval, 0.89–0.92; P < .001). A mixed-effects model showed that in this population 94% of the variation in salivary cortisone could be predicted from serum cortisol. Conclusion: Salivary cortisol is frequently undetectable and contaminated by oral hydrocortisone. In contrast, salivary cortisone reflects serum cortisol and provides a noninvasive alternative to measuring serum cortisol levels.
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2

Meulenberg, P. M., and J. A. Hofman. "Differences between concentrations of salivary cortisol and cortisone and of free cortisol and cortisone in plasma during pregnancy and postpartum." Clinical Chemistry 36, no. 1 (January 1, 1990): 70–75. http://dx.doi.org/10.1093/clinchem/36.1.70.

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Abstract We measured cortisol and cortisone in plasma--both total and free--and in saliva during the course of pregnancy and postpartum. Antepartum and postpartum concentrations and morning and afternoon concentrations of both steroids were compared. The mean concentrations of cortisol and cortisone increased towards term and were significantly greater at the end of pregnancy than postpartum, except for free cortisol in plasma in the afternoon. The daily rhythm of both steroids was maintained throughout pregnancy and postpartum. The correlations between salivary and plasma free concentrations of cortisol and cortisone as well as of the sum of cortisol + cortisone were highly significant. The mean concentrations of cortisone in saliva accurately reflected both total and free concentrations in plasma. For cortisol, however, the change of the concentrations in saliva, was somewhat different from that in plasma. Moreover, the mass ratio of plasma free cortisol to salivary cortisol was about 2, whereas for cortisone the ratio was only about 0.5, probably owing to the conversion of cortisol to cortisone by 11 beta-hydroxysteroid dehydrogenase in the salivary gland. Furthermore, the passage of cortisol and cortisone from plasma to saliva should not be regarded as simple diffusion, because in the first half of pregnancy the sum of the concentrations of cortisol + cortisone in saliva significantly exceeded the sum of their free concentrations in plasma.
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3

Žaja, Roko, Sanja Stipičević, Milan Milošević, Andro Košec, Jakov Ajduk, Iva Kelava, Adrijana Zglavnik Baća, Marko Klarica, and Mihael Ries. "Salivary cortisone as potential predictor of occupational exposure to noise and related stress." Archives of Industrial Hygiene and Toxicology 74, no. 4 (December 1, 2023): 232–37. http://dx.doi.org/10.2478/aiht-2023-74-3785.

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Abstract Salivary cortisone strongly correlates with serum cortisol, and since it is less invasive to measure salivary cortisone than serum cortisol and easier than to measure cortisol in saliva, as its concentrations are much lower, we wanted to compare salivary cortisone and cortisol levels as markers of noise-induced stress reaction. The study included 104 participants aged 19–30 years, 50 of whom were exposed to occupational noise ≥85 dB(A) and 54 non-exposed, control students. All participants took samples of their saliva with Salivette® Cortisol synthetic swabs on three consecutive working days first thing in the morning. Salivary cortisone and cortisol levels were determined with high-performance liquid chromatography. In addition, they completed a 10-item Perceived Stress Scale (PSS-10) questionnaire, and occupationally noise-exposed participants also completed the Health and Safety Executive (HSE) questionnaire on occupational psychosocial risks. The exposed participants had significantly higher cortisone (P<0.001) and cortisol (P<0.001) levels than controls, and the correlation between cortisone and cortisol levels in the exposed participants was strong (ϱ =0.692, P<0.001), which suggests that salivary cortisone can replace cortisol measurements in saliva as a more reliable method than salivary cortisol and less invasive than serum cortisol. However, the level of perceived stress scored on PSS-10 in the exposed participants did not differ significantly from stress reported by controls, but correlated negatively with cortisone levels, which is contrary to our expectations and raises questions as to why.
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4

Colling, Caitlin, Miriam Bredella, Pouneh Fazeli, Gisela Pachón-Peña, Ravinder Singh, Anne Klibanski, Clifford Rosen, and Karen Miller. "ODP053 Serum Free Cortisol and Free Cortisol-to-Cortisone Ratio Increase After 10 Days of Overfeeding and After 10 Days of Fasting." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A64—A65. http://dx.doi.org/10.1210/jendso/bvac150.132.

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Abstract Introduction Chronic caloric deprivation and obesity are complicated by elevations of serum total cortisol levels. The effects of acute overfeeding and fasting on circulating free cortisol levels and interconversion of cortisone to free cortisol are unknown. We hypothesized that serum free cortisol and free cortisol-to-cortisone ratio (a surrogate measure of 11β-hydroxysteroid dehydrogenase [11β-HSD] activity) would increase after both overfeeding and fasting. Methods We prospectively studied 22 healthy volunteers who underwent a 10-day high-calorie protocol followed by a 10-day fast, separated by a 2-week wash-out period, in a Clinical Research Center. Fasting morning free and total cortisol and free cortisone levels (liquid chromatography-tandem mass spectrometry, Mayo Labs) and percent body fat (dual-energy x-ray absorptiometry) were performed at baseline before and after 10 days of each intervention. Results High-calorie feeding increased total and free cortisol and the free cortisol-to-free cortisone ratio (p&lt;0. 001 to p=0. 046). Total and free cortisol, the free cortisol-to-free cortisone ratio, and the free cortisol-to-total cortisol ratio increased after fasting (p=0. 001 to 0. 021). During the high-calorie protocol, there was no significant interaction between sex and time for any of the cortisol parameters. During the fasting visit, the changes in free cortisol and free-to-total cortisol ratio were modified by sex (p=0. 014 and 0. 004, respectively for interaction term), with a trend toward a significant interaction between sex and time in the change in free cortisol-to-free cortisone ratio (p=0. 054). In subset analyses stratified by sex examining the effect of fasting on free cortisol and the free-to-total cortisol ratio, there were significant increases in men (p&lt;0. 001) but not women (p=0.898 and 1. 000, respectively). Baseline percent body fat, measured at the start of the fasting visit, was inversely associated with change in free cortisol (ρ=-0.52, p=0. 013), free cortisol-to-total cortisol ratio (ρ=-0.49, p=0. 021) and free cortisol-to-cortisone ratio (ρ=-0.47, p=0. 029) during fasting. Conclusion Overfeeding and fasting both increase circulating free cortisol levels and appear to alter 11β-HSD activity. The effect of fasting, but not overfeeding, on free cortisol levels is modified by sex. Greater percent fat mass may be relatively protective against starvation-induced hypercortisolemia in women. Further study is warranted to determine whether elevated cortisol levels contribute to complications of starvation and obesity, such as bone fragility. Presentation: No date and time listed
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5

Harrison, Robert F., Miguel Debono, Martin J. Whitaker, Brian G. Keevil, John Newell-Price, and Richard J. Ross. "Salivary Cortisone to Estimate Cortisol Exposure and Sampling Frequency Required Based on Serum Cortisol Measurements." Journal of Clinical Endocrinology & Metabolism 104, no. 3 (October 3, 2018): 765–72. http://dx.doi.org/10.1210/jc.2018-01172.

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Abstract Context Population studies frequently measure cortisol as a marker of stress, and excess cortisol is associated with increased mortality. Cortisol has a circadian rhythm, and frequent blood sampling is impractical to assess cortisol exposure. We investigated measuring salivary cortisone and examined the sampling frequency required to determine cortisol exposure. Methods Serum and saliva with cortisol and cortisone were measured by liquid chromatography–tandem mass spectrometry in independent cohorts. The relationship between serum cortisol and salivary cortisone was analyzed in cohort 1 using a linear mixed effects model. The resulting fixed effects component was applied to cohort 2. Saliva cannot easily be collected when a patient is sleeping, so we determined the minimum sampling required to estimate cortisol exposure [estimated area under the curve (eAUC)] using 24-hour cortisol profiles (AUC24) and calculated the relative error (RE) for eAUC. Results More than 90% of variability in salivary cortisone could be accounted for by change in serum cortisol. A single serum cortisol measurement was a poor estimate of AUC24, especially in the morning or last thing at night (RE &gt;68%); however, three equally spaced samples gave a median RE of 0% (interquartile range, −15.6% to 15.1%). In patients with adrenal incidentalomas, eAUC based on three serum cortisol samples showed a difference between those with autonomous cortisol secretion and those without (P = 0.03). Interpretation Accepting that most people sleep 7 to 8 hours, ∼8-hourly salivary cortisone measurements provide a noninvasive method of estimating 24-hour cortisol exposure for population studies.
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Quilez, Ester, Richard K. Burchell, Eric B. Thorstensen, Karin Weidgraaf, Stacey E. Parbhu, Nicolas Lopez-Villalobos, and Arnon Gal. "Cortisol urinary metabolites in dogs with hypercortisolism, congestive heart failure, and healthy dogs: pilot investigation." Journal of Veterinary Diagnostic Investigation 32, no. 2 (January 10, 2020): 317–23. http://dx.doi.org/10.1177/1040638719899645.

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Nonadrenal diseases (NAD), including congestive heart failure (CHF), can affect the conversion of cortisone to cortisol favoring the production of cortisol’s urinary downstream metabolites 5α/5β-tetrahydrocortisol (THF) relative to tetrahydrocortisone (THE). We hypothesized that healthy dogs would have lower urinary levels of cortisol, cortisone, THF, and THE than dogs with hypercortisolism (HC) or CHF, and the latter would have higher urinary levels of THF and lower THE than dogs with HC. Four, 9, and 8 dogs with HC, CHF, and normal health, respectively, were included in a pilot prospective cross-sectional study. A single morning voided urine sample was analyzed for urinary cortisol metabolites by liquid chromatography–mass spectrometry. The percentages of conjugated urinary metabolites were significantly higher in dogs with CHF than in healthy dogs ( p = 0.001), and not different in HC dogs ( p = 0.07). Log-transformed urine cortisol metabolites–to–creatinine ratios in healthy dogs were significantly lower than the 2 other groups ( p < 0.001). The urinary free THE:THF ratio was significantly higher ( p < 0.001) than the urinary total and conjugated THE:THF ratios. Health status did not affect the total, conjugated, and free THE:THF ratios ( p = 0.61). Additional studies are needed to investigate differences in cortisol metabolites between dogs with HC and NAD to accurately discriminate between the groups.
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7

Raff, Hershel, and James W. Findling. "Salivary cortisol or cortisone?" Nature Reviews Endocrinology 6, no. 12 (November 23, 2010): 658–60. http://dx.doi.org/10.1038/nrendo.2010.192.

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8

Nomura, Shinji, Michiko Fujitaka, Nobuo Sakura, and Kazuhiro Ueda. "Circadian rhythms in plasma cortisone and cortisol and the cortisone/cortisol ratio." Clinica Chimica Acta 266, no. 2 (October 1997): 83–91. http://dx.doi.org/10.1016/s0009-8981(97)00142-3.

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9

Sigurjonsdottir, Helga A., Ruth Andrew, Roland H. Stimson, Gudmundur Johannsson, and Brian R. Walker. "Lack of regulation of 11β-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism." European Journal of Endocrinology 161, no. 3 (September 2009): 375–80. http://dx.doi.org/10.1530/eje-09-0315.

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ObjectiveEvidence from long-term clinical studies measuring urinary steroid ratios, and from in vitro studies, suggests that GH administered for longer than 2 months down-regulates 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), thereby reducing cortisol regeneration in liver and adipose tissue. We aimed to measure acute effects of GH on 11β-HSD1 in liver and adipose tissue in vivo, including using a stable isotope tracer.DesignObservational studies of GH withdrawal and reintroduction in patients with hypopituitarism.MethodsTwelve men with benign pituitary disease causing GH and ACTH deficiency on stable replacement therapy for >6 months were studied after GH withdrawal for 3 weeks, and after either placebo or GH injections were reintroduced for another 3 weeks. We measured cortisol kinetics during 9,11,12,12-2H4-cortisol (d4-cortisol) infusion, urinary cortisol/cortisone metabolite ratios, liver 11β-HSD1 by appearance of plasma cortisol after oral cortisone, and 11β-HSD1 mRNA levels in subcutaneous adipose biopsies.ResultsGH withdrawal and reintroduction had no effect on 9,12,12-[2H]3-cortisol (d3-cortisol) appearance, urinary cortisol/cortisone metabolite ratios, initial appearance of cortisol after oral cortisone, or adipose 11β-HSD1 mRNA. GH withdrawal increased plasma cortisol 30–180 min after oral cortisone, increased d4-cortisol clearance, and decreased relative excretion of 5α-reduced cortisol metabolites.ConclusionsIn this setting, GH did not regulate 11β-HSD1 rapidly in vivo in humans. Altered cortisol metabolism with longer term changes in GH may reflect indirect effects on 11β-HSD1. These data do not suggest that glucocorticoid replacement doses need to be increased immediately after introducing GH therapy to compensate for reduced 11β-HSD1 activity, although dose adjustment may be required in the longer term.
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10

Kalaria, Tejas, Mayuri Agarwal, Sukhbir Kaur, Lauren Hughes, Hayley Sharrod-Cole, Rahul Chaudhari, Carolina Gherman-Ciolac, et al. "Hypothalamic–pituitary–adrenal axis suppression – The value of salivary cortisol and cortisone in assessing hypothalamic–pituitary–adrenal recovery." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 57, no. 6 (October 13, 2020): 456–60. http://dx.doi.org/10.1177/0004563220961745.

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Background The 0.25 mg short synacthen test is used to assess recovery from hypothalamic–pituitary–adrenal suppression due to chronic glucocorticoid administration. We assessed the potential role of salivary cortisol and cortisone in predicting hypothalamic–pituitary–adrenal function using the short synacthen test as the gold standard test. Method Between 09:00 and 10:30, salivary and blood samples were collected just prior to a short synacthen test to assess hypothalamic–pituitary–adrenal axis recovery in patients previously treated with oral glucocorticoids. The cut-off for a normal short synacthen test was a 30-min cortisol ≥450 nmol/L. Results Fifty-six short synacthen tests were performed on 47 patients. Of these, 15 were normal. The area under receiver operating characteristic curves for serum cortisol, salivary cortisone and salivary cortisol were 0.772, 0.785 and 0.770, respectively. From the receiver operating characteristic analysis, the cut-offs for baseline serum cortisol (≥365 nmol/L) and salivary cortisone (≥37.2 nmol) predicted hypothalamic–pituitary–adrenal axis recovery with 100% specificity in 26.7% of pass short synacthen tests, whereas salivary cortisol predicted none. Baseline serum cortisol (≤170 nmol/L), salivary cortisone (≤9.42 nmol/L) and salivary cortisol (≤1.92 nmol/L) predicted hypothalamic–pituitary–adrenal suppression with 100% sensitivity in 58.5%, 53.7% and 51.2% of failed short synacthen tests, respectively. Using these cut-offs, baseline serum cortisol, salivary cortisone and salivary cortisol could reduce the need for short synacthen tests by 50%, 46% and 37%, respectively. Conclusion Although marginally inferior to early morning serum cortisol, early morning salivary cortisone may be used as a first-line test for assessing hypothalamic–pituitary–adrenal function. We plan to incorporate salivary cortisone into a home-based patient pathway to identify patients with hypothalamic–pituitary–adrenal recovery, continuing hypothalamic–pituitary–adrenal suppression and those who require a short synacthen test.
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Taylor, Robert L., Dwaine Machacek, and Ravinder J. Singh. "Validation of a High-Throughput Liquid Chromatography–Tandem Mass Spectrometry Method for Urinary Cortisol and Cortisone." Clinical Chemistry 48, no. 9 (September 1, 2002): 1511–19. http://dx.doi.org/10.1093/clinchem/48.9.1511.

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Abstract Background: Urinary free cortisol and cortisone measurements are useful in evaluation of Cushing syndrome, apparent mineralocorticoid excess, congenital adrenal hyperplasia, and adrenal insufficiency. To reduce analytical interference, improve accuracy, and shorten the analysis time, we developed a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for urinary cortisol and cortisone. Methods: We added 190 pmol (70 ng) of stable isotope cortisol-9,11,12,12-d4 to 0.5 mL of urine as an internal standard before extraction. The urine was extracted with 4.5 mL of methylene chloride, washed, and dried, and 10 μL of the reconstituted extract was injected onto a reversed-phase C18 column and analyzed using a tandem mass spectrometer operating in the positive mode. Results: Multiple calibration curves for urinary cortisol and cortisone exhibited consistent linearity and reproducibility in the range 7–828 nmol/L (0.25–30 μg/dL). Interassay CVs were 7.3–16% for mean concentrations of 6–726 nmol/L (0.2–26.3 μg/dL) for cortisol and cortisone. The detection limit was 6 nmol/L (0.2 μg/dL). Recovery of cortisol and cortisone added to urine was 97–123%. The regression equation for the LC-MS/MS (y) and HPLC (x) method for cortisol was: y = 1.11x + 0.03 μg cortisol/24 h (r2 = 0.992; n = 99). The regression equation for the LC-MS/MS (y) and immunoassay (x) methods for cortisol was: y = 0.66x − 12.1 μg cortisol/24 h (r2 = 0.67; n = 99). Conclusion: The sensitivity and specificity of the LC-MS/MS method for urinary free cortisol and cortisone offer advantages over routine immunoassays or chromatographic methods because of elimination of drug interferences, high throughput, and short chromatographic run time.
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Kennedy, Emily K. C., and David M. Janz. "First Look into the Use of Fish Scales as a Medium for Multi-Hormone Stress Analyses." Fishes 7, no. 4 (June 23, 2022): 145. http://dx.doi.org/10.3390/fishes7040145.

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Recent efforts have provided convincing evidence for the use of fish scale cortisol concentration in the assessment of long-term stress in fishes. However, cortisol alone is not sufficient to fully describe this state of long-term stress. Dehydroepiandrosterone (DHEA) is an androgen with actions that oppose those of cortisol. The means by which DHEA negates the effects of cortisol occurs in part via changes in the metabolism of cortisol to cortisone. The quantitation of cortisol, DHEA and cortisone could therefore provide a more comprehensive assessment of the overall status of physiological stress. As DHEA and cortisone have yet to be quantified within the fish scale, our first objective was to ensure our sample processing protocol for cortisol was applicable to cortisone and DHEA. Following this, we induced a state of long-term stress in goldfish (Carassius auratus). Some degree of elevation in all hormones was observed in the stressed fish scales. Additionally, cortisol and cortisone were significantly elevated in the stressed fish serum in comparison to controls while DHEA was undetectable in either group. Overall, these results suggest that fish scales provide an appropriate medium for the assessment of long-term stress in fishes via the quantitation of relevant steroid hormones.
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Yang, Zhen, Chunming Guo, Ping Zhu, Wenjiao Li, Leslie Myatt, and Kang Sun. "Role of glucocorticoid receptor and CCAAT/enhancer-binding protein α in the feed-forward induction of 11β-hydroxysteroid dehydrogenase type 1 expression by cortisol in human amnion fibroblasts." Journal of Endocrinology 195, no. 2 (November 2007): 241–53. http://dx.doi.org/10.1677/joe-07-0303.

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The amount of cortisol available to its receptors is increased by the pre-receptor enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which converts cortisone to cortisol. We examined the molecular mechanisms of the feedback effect of cortisol on 11β-HSD1 mRNA expression in human amnion fibroblasts. Our data showed that cortisol-induced 11β-HSD1 mRNA expression dose dependently in amnion fibroblasts, which could be completely blocked both by the mRNA transcription inhibitor 5,6-dichlorobenzimidazole riboside and by the glucocorticoid receptor (GR) antagonist RU486, and partially blocked by global inhibition of CCAAT/enhancer-binding proteins (C/EBPs) with transfection of C/EBP-specific dominant-negative expression CMV500 plasmid (AC/EBP) into the cells. Likewise, the induction of the promoter activity by cortisol could also be completely blocked by RU486 and partially by AC/EBP transfection. Progressive 5′ deletion of the 11β-HSD1promoter located the region responsible for cortisol’s induction within −204 bp upstream to the transcription start site. Specific nucleotide mutations of the putative glucocorticoid responsive element or CCAAT in this promoter region attenuated the induction by cortisol. Moreover, chromatin immunoprecipitation assay and electrophoretic mobility shift assay showed that GR and C/EBPα but not C/EBPβ could bind this promoter region upon cortisol stimulation of amnion fibroblasts. In conclusion, we demonstrated that GR and C/EBPα were involved in cortisol-induced 11β-HSD1 mRNA expression via binding to 11β-HSD1 promoter in amnion fibroblasts, which may cast a feed-forward production of cortisol in the fetal membranes at the end of gestation.
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Panigrahi, Sunil K., Cristina D. Toedesbusch, Jennifer S. McLeland, Brendan P. Lucey, and Sharon L. Wardlaw. "Diurnal Patterns for Cortisol, Cortisone and Agouti-Related Protein in Human Cerebrospinal Fluid and Blood." Journal of Clinical Endocrinology & Metabolism 105, no. 4 (December 15, 2019): e1584-e1592. http://dx.doi.org/10.1210/clinem/dgz274.

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Abstract Context Cortisol in blood has a robust circadian rhythm and exerts potent effects on energy balance that are mediated in part by central mechanisms. These interactions involve orexigenic agouti-related protein (AgRP) neurons that are stimulated by glucocorticoids. However, diurnal changes in brain or cerebrospinal fluid (CSF) cortisol and cortisone, which are interconverted by 11ß-HSD1, have not been characterized in humans. Objective To conduct a secondary analysis of existing samples to characterize diurnal changes in cortisol and cortisone in CSF and examine their relationships to changes in AgRP. Methods Stored CSF and plasma samples were obtained from 8 healthy subjects who served as controls for a sleep study. CSF was collected every 2h for 36h via indwelling lumbar catheter; plasma was collected every 2h. Results There was a diurnal rhythm for cortisol and cortisone in CSF that closely followed the plasma rhythm by 2 h with peak and nadir levels at 0900h and 0100h. The ratio of cortisol (active) to cortisone (inactive) in CSF was 48% higher at the peak versus nadir. There was a diurnal rhythm for AgRP in plasma that was out of phase with the cortisol rhythm. There was a less distinct diurnal rhythm for AgRP in CSF that oscillated with a similar phase as cortisol. Conclusions There is a robust diurnal rhythm for cortisol and cortisone in CSF. Diurnal changes were noted for AgRP that are related to the cortisol changes. It remains to be determined if AgRP mediates adverse metabolic effects associated with disruption of the cortisol circadian rhythm.
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VAN UUM, Stan H. M., Brian R. WALKER, Ad R. M. M. HERMUS, C. G. J. (Fred) SWEEP, Paul SMITS, Peter W. DE LEEUW, and Jacques W. M. LENDERS. "Effect of glycyrrhetinic acid on 11β-hydroxysteroid dehydrogenase activity in normotensive and hypertensive subjects." Clinical Science 102, no. 2 (January 11, 2002): 203–11. http://dx.doi.org/10.1042/cs1020203.

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The 11β-hydroxysteroid dehydrogenase (11β-HSD) isoenzymes catalyse the interconversion of cortisol and cortisone. Type 1 11β-HSD mainly converts cortisone into active cortisol. Type 2 11β-HSD inactivates cortisol in mineralocorticoid target tissues, and its activity can be inhibited by glycyrrhetinic acid (GA). Inactivation of cortisol to cortisone is impaired in a subgroup of patients with primary hypertension. To study where this defect is located, we measured cortisol and cortisone concentrations in arterial plasma, in saliva and across the forearm at baseline and after administration of GA in normotensive and hypertensive subjects. GA (500mg) or placebo was administered orally to 20 normotensive subjects in a placebo-controlled double-blind fashion. Further, we compared the effect of GA in 20 patients with primary hypertension with that in 20 normotensive subjects. Cortisol and cortisone were measured in plasma from the brachial artery and vein and in saliva. Samples were obtained at 0, 90 and 150min. Forearm blood flow (FBF) was measured simultaneously. Forearm production of corticosteroid hormones was assessed by multiplying the arteriovenous difference in corticosteroid concentration by FBF. The cortisol/cortisone ratio in arterial plasma remained at baseline levels after placebo (4.9±1.2; mean±S.D.), while after GA the ratio increased similarly in normotensive subjects (12.3±3.4) and in hypertensive patients (12.2±3.7). A similar effect of GA on the salivary cortisol/cortisone ratio was found. In both normotensive subjects and hypertensive patients no forearm production of cortisol or cortisone could be demonstrated, either at baseline or after administration of GA. Thus, both before and after GA administration, we did not find any difference in systemic and salivary 11β-HSD type 2 activity between subjects with primary hypertension and normotensive controls. Further, both at baseline and after GA administration we were not able to demonstrate net inactivation or re-activation of cortisol and cortisone by the 11β-HSD isoenzymes in the forearm in either normotensive or primary hypertensive subjects.
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Bäcklund, Nils, Göran Brattsand, Marlen Israelsson, Oskar Ragnarsson, Pia Burman, Britt Edén Engström, Charlotte Høybye, et al. "Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing’s syndrome." European Journal of Endocrinology 182, no. 6 (June 2020): 569–82. http://dx.doi.org/10.1530/eje-19-0872.

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Objective The challenge of diagnosing Cushing’s syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST). Design and methods Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves. Results The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70–99%) and specificity of 96% (91–98%) for cortisol, and a 100% (84–100%) sensitivity and 95% (90–98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75–100%) sensitivity and 96% (92–99%) specificity with cortisol, and 100% (83–100%) sensitivity and 94% (89–97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h. Conclusion Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.
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Webb, Rachel J., Neera Sunak, Lisa Wren, and Anthony E. Michael. "Inactivation of glucocorticoids by 11β-hydroxysteroid dehydrogenase enzymes increases during the meiotic maturation of porcine oocytes." REPRODUCTION 136, no. 6 (December 2008): 725–32. http://dx.doi.org/10.1530/rep-08-0289.

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Recent reports have shown that glucocorticoids can modulate oocyte maturation in both teleost fish and mammals. Within potential target cells, the actions of physiological glucocorticoids are modulated by 11β-hydroxysteroid dehydrogenase (HSD11B) isoenzymes that catalyse the interconversion of cortisol and cortisone. Hence, the objective of this study was to establish whether HSD11B enzymes mediate cortisol–cortisone metabolism in porcine oocytes and, if so, whether the rate of glucocorticoid metabolism changes during oocyte maturation. Enzyme activities were measured in cumulus–oocyte complexes (COCs) and denuded oocytes (DOs) using radiometric conversion assays. While COCs and DOs oxidised cortisol to inert cortisone, there was no detectable regeneration of cortisol from cortisone. The rate of cortisol oxidation was higher in expanded COCs than in compact COCs containing germinal vesicle (GV) stage oocytes (111±6 vs 2041±115 fmol cortisone/oocyte.24 h; P<0.001). Likewise, HSD11B activities were 17±1 fold higher in DOs from expanded COCs than in those from compact COCs (P<0.001). When GV stage oocytes were subject to a 48 h in vitro maturation protocol, the enzyme activities were significantly increased from 146±18 to 1857±276 fmol cortisone/oocyte.24 h in GV versus MII stage oocytes respectively (P<0.001). Cortisol metabolism was inhibited by established pharmacological inhibitors of HSD11B (glycyrrhetinic acid and carbenoxolone), and by porcine follicular and ovarian cyst fluid. We conclude that an HSD11B enzyme (or enzymes) functions within porcine oocytes to oxidise cortisol, and that this enzymatic inactivation of cortisol increases during oocyte maturation.
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Yang, Yi, Jiachen Shi, Jie Yin, Yunjia Yang, Bing Shao, and Jing Zhang. "Occurrence and Estimated Daily Intake of Cortisone and Cortisol in Aquatic Food from China TDS." Foods 11, no. 21 (November 2, 2022): 3481. http://dx.doi.org/10.3390/foods11213481.

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Glucocorticoids (GCs) widely exist in animal food including aquatic food. This study aimed to survey the occurrences of cortisone and cortisol in aquatic food and the estimated daily intake (EDI) of cortisone and cortisol due to different habits of aquatic food consumption. The mean levels of cortisone and cortisol in freshwater fish purchased from market were 14.59 μg/kg and 69.15 μg/kg, respectively, which were markedly higher than the levels in marine fish. A test using Zebrafish was performed to compare the concentration of GCs by different killing methods. The results suggested that physically traumatic killing methods are one of the reasons why the levels of GCs in freshwater fish were higher than those in marine fish. The concentrations of cortisone and cortisol in composite aquatic food samples from 12 provincial districts of the fourth China Total Diet Study (TDS) were 0.72~15.75 μg/kg and 4.90~66.13 μg/kg, respectively, which were positively correlated with the distance from the coastline. Further, the correlation coefficient between the levels of cortisone and cortisol in aquatic food and the percentages of freshwater fish consumption were 0.758 (p < 0.01) and 0.908 (p < 0.01), respectively. There was a significant positive correlation between the levels of cortisone and cortisol in aquatic food in the fourth TDS and the percentages of freshwater fish consumption. The calculated average EDIs of cortisone and cortisol from aquatic food in the fourth TDS were 0.16 μg/d and 0.72 μg/d, respectively.
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Dreyer, Anja Fenger, Richard Christian Jensen, Dorte Glintborg, Anne Vibeke Schmedes, Ivan Brandslund, Flemming Nielsen, Henriette Boye Kyhl, Tina Kold Jensen, and Marianne Skovsager Andersen. "Perfluoroalkyl Substance Exposure Early In Pregnancy Was Negatively Associated With Late Pregnancy Cortisone Levels." Journal of Clinical Endocrinology & Metabolism 105, no. 8 (May 21, 2020): e2834-e2844. http://dx.doi.org/10.1210/clinem/dgaa292.

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Abstract Introduction During pregnancy, maternal cortisol levels are increased 3-fold by the third trimester. The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD, isoforms 1 and 2) regulates the balance between cortisol and cortisone levels. Perfluoroalkyl substances (PFAS) have been reported to inhibit 11β-HSD1 and more potently 11β-HSD2, which could lead to reduced levels of cortisol and more extensively cortisone. Aim The aim of this work is to investigate a possible effect of early pregnancy PFAS exposure on late pregnancy activity of 11β-HSD1 and 11β-HSD2 assessed by cortisol and cortisone levels in diurnal urine (dU) and blood samples. Methods This study is part of the prospective cohort study, Odense Child Cohort (OCC). A total of 1628 pregnant women had serum (S) concentrations of 5 PFAS (perfluorooctanoic acid [PFOA], perfluorooctane sulfonic acid [PFOS], perfluorohexane sulfonic acid [PFHxS], perfluorononanoic acid [PFNA], and perfluorodecanoic acid (PFDA)) measured in the first trimester (median gestational week, GW 11). dU cortisol and cortisone (n = 344) and S-cortisol (n = 1048) were measured in the third trimester (median GW 27). Results In multiple regression analyses, a 2-fold increase in S-PFOS was significantly associated with lower dU-cortisone (β = –9.1%, P &lt; .05) and higher dU-cortisol/dU-cortisone (dU-C/C) (β = 9.3%, P &lt; .05). In crude models, a doubling in PFOS, PFOA, PFHxS, and PFNA concentrations were associated with a significant increase in S-cortisol; however, these associations became insignificant after adjustment. Conclusion Early pregnancy maternal S-PFAS were inversely associated with late pregnancy dU-cortisone, indicating reduced activity of 11β-HSD2.
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Kertys, Martin, Anna Urbanova, Michal Mestanik, Ingrid Tonhajzerova, and Juraj Mokry. "Simultaneous Determination of Total Cortisol and Cortisone in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry: Method Development, Validation and Preliminary Clinical Application." Current Pharmaceutical Analysis 15, no. 4 (March 19, 2019): 363–70. http://dx.doi.org/10.2174/1573412914666180427094811.

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Background:Cortisol as a major glucocorticosteroid product of the adrenal cortex which has been recognized as a stress biomarker in evaluating stress related disorders for a long time. Plasma concentration of cortisol and its metabolite cortisone are usually changed in physiological and psychological tension, anxiety and depression. In order to study these changes properly, we need a sensitive, accurate and reproducible assay for plasma cortisol and cortisone determination. </P><P> Objective: The aim of this study was to develop a sensitive and robust method for the determination of total cortisol and cortisone in human plasma using mass spectrometry.Methods:A fast, sensitive and selective liquid chromatography-tandem mass spectrometry (LCMS/ MS) method was developed, validated, and then the levels of cortisol and cortisone were determined. Plasma samples cleanup procedure was composed of two steps: the first was a protein precipitation with 1 % formic acid in acetonitrile, and the second was an on-line solid phase extraction (SPE). Afterwards, cortisol and cortisone were separated using a C18 ACQUITY UPLC BEHTM column with a gradient elution. The mobile phase A was 0.1 % formic acid in water, the mobile phase B was 0.1 % methanol. For the detection we used a XEVO TQ-S mass spectrometer operating in the ESI positive mode.Results:The time of analysis was 6.5 minutes and the quantification range was 5-600 ng/mL for cortisol and cortisone, with > 94% recovery for all analytes (cortisol, cortisone and internal standards). The method was validated according to the EMA guideline for bioanalytical method validation.Conclusion:A simple and sensitive LC-MS/MS method was developed and validated for measurement of cortisol and cortisone in human plasma. Our findings indicate that the proposed analytical method is suitable for routine analysis.
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Tulloh, RMR, FF Quek, K. Stevenson, V. Garratt, and JM Turner-Cobb. "Cortisol/cortisone levels and quality of life in individuals with pulmonary arterial hypertension." Pulmonary Circulation 10, no. 2 (April 2020): 204589402092432. http://dx.doi.org/10.1177/2045894020924325.

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Individuals with pulmonary arterial hypertension experience debilitating symptoms and psychological distress which may influence their cortisol regulation. We describe associations between diurnal salivary cortisol/cortisone levels and quality of life in adults with pulmonary arterial hypertension. Findings suggest potential clinical utility of cortisol/cortisone assessment as applied to a pulmonary arterial hypertension population.
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Jiménez-Castro, Mónica B., Elsa Negrete-Sánchez, Araní Casillas-Ramírez, Jose Gulfo, Ana I. Álvarez-Mercado, María Eugenia Cornide-Petronio, Jordi Gracia-Sancho, Juan Rodés, and Carmen Peralta. "The effect of cortisol in rat steatotic and non-steatotic liver transplantation from brain-dead donors." Clinical Science 131, no. 8 (April 6, 2017): 733–46. http://dx.doi.org/10.1042/cs20160676.

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In the present study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with up-regulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were down-regulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation (LT); however, cortisol treatment up-regulated the phosphoinositide 3-kinase (PI3K)–protein kinase C (PKC) pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic LT as well as in increased survival of recipients. The present study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts.
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Skarlandtová, Hana, Marie Bičíková, Petr Neužil, Mikuláš Mlček, Vladimír Hrachovina, Tomáš Svoboda, Eva Medová, et al. "The Cortisol to Cortisone Ratio during Cardiac Catheterisation in Sows." Prague Medical Report 116, no. 4 (2015): 279–89. http://dx.doi.org/10.14712/23362936.2015.67.

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A possible effect of mini-invasive heart intervention on a response of hypothalamo-pituitary-adrenal stress axis and conversion of cortisone to cortisol were studied. We have analysed two stress markers levels (cortisol, cortisone) and cortisol/cortisone ratio in 25 sows using minimally invasive heart catheterisation as the stress factor. The values of studied parameters were assessed in four periods of the experiment: (1) the baseline level on the day before intervention, (2) after the introduction of anaesthesia, (3) after conducting tissue stimulation or ablation, and (4) after the end of the catheterisation. For statistical analyses we used the non-parametric Friedman test for four dependent samples (including all four stages of the operation) or three dependent samples (influence of operation only, baseline level was excluded). Statistically significant differences in both Friedman tests were found for cortisol and for cortisone. We have found the highest level of cortisol/cortisone ratio in unstressed conditions, then it decreased to the minimal level at the end of the intervention. We have concluded that cortisol levels are blunted by the influence of anaesthesia after its administration, and therefore decrease back to the baseline at the end of the operation.
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Alvi, Syed N., Kafa Abuhdeeb, and Muhammad M. Hammami. "Sweat Cortisol and Cortisone Determination in Healthy Adults: UHPLC-MS/MS Assay Validation and Clinical Application." Advances in Pharmacological and Pharmaceutical Sciences 2022 (November 29, 2022): 1–5. http://dx.doi.org/10.1155/2022/3133640.

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A simple and effective ultra-high-performance liquid chromatography assay linked to tandem mass spectrometry (UHPLC-MS/MS) for measuring cortisol and cortisone levels in human sweat has been developed and validated. A noninvasive world standard sweat collecting equipment was utilized to collect samples. The samples were analyzed using an Atlantis dC18 (2.1 × 100 mm, 3 μm) column with a 2 mM ammonium acetate and acetonitrile (1 : 1, v : v) mobile phase. In an isocratic condition, the mobile phase was delivered at a flow rate of 0.3 ml/minute. A positive electrospray ionization interface with multiple-reaction monitoring mode was used to provide simultaneous quantification of cortisol, cortisone, and internal standard at transitions of 363.11 to 121.00, 361.18 to 163.11, and 367.19 to 121.24, respectively. The method was validated for cortisol and cortisone determination over a concentration range of 0.5–50 ng/mL The detection limits for cortisol and cortisone in human sweat were 0.3 and 0.2 ng/ml, respectively. The interday coefficients of variation of cortisol and cortisone were ≤8.5% and ≤10.01%, whereas bias was in the range from −7.9% to 2.1% and from −4.3% to 3.0%, respectively. The assay was successfully applied to evaluate the cortisol-to-cortisone ratio in sweat samples collected from healthy adult volunteers.
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Raff, Hershel, and Jonathan M. Phillips. "Bedtime Salivary Cortisol and Cortisone by LC-MS/MS in Healthy Adult Subjects: Evaluation of Sampling Time." Journal of the Endocrine Society 3, no. 8 (June 26, 2019): 1631–40. http://dx.doi.org/10.1210/js.2019-00186.

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AbstractThe measurement of late-night salivary cortisol is a mainstay in the diagnosis of Cushing syndrome. Furthermore, the measurement of salivary cortisol is useful in assessing the cortisol awakening response. Because the salivary glands express 11-β-hydroxysteroid dehydrogenase, the measurement of salivary cortisone may improve the performance of salivary corticosteroid measurements. We measured salivary cortisol by enzyme immunoassay (EIA) and salivary cortisol and cortisone by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in only 50 µL of saliva sampled from 54 healthy subjects (aged 20 to 64 years). We allowed patients to sample at their normal bedtime (2025 to 2400 hours) to answer a common question as to whether sampling at the normal bedtime is equivalent to the standard required sampling at 2300 to 2400 hours. We found that the salivary cortisol and cortisone results by LC-MS/MS correlated well with salivary cortisol measured with the US Food and Drug Administration-cleared EIA. Furthermore, the upper limit of normal of salivary cortisol by EIA for bedtime samples was lower than the previously published upper limit of normal with sampling required at 2300 to 2400 hours. There were no significant effects of age or sex on any of the salivary steroid measurements. We conclude that (i) salivary cortisol and cortisone can be reliably measured by LC-MS/MS in small volumes of saliva and (ii) that patients can be evaluated using saliva sampled at their normal bedtime, rather than being required to stay awake until 2300 to 2400 hours.
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Chen, Binbin, Haiyan Lyu, Xiangzhen Xu, and Chen Wang. "Simultaneous quantification of cortisol and cortisone in serums and saliva from depressive patients by supported liquid extraction coupled to HPLC–MS/MSs." Acta Chromatographica 32, no. 4 (December 2020): 269–75. http://dx.doi.org/10.1556/1326.2020.00733.

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Cortisol and cortisone are 2 important glucocorticoids produced in the human hypothalamus–pituitary–adrenal (HPA) axis that respond to stress. An analytical method to determinate cortisol and cortisone in serum and saliva using high-performance liquid chromatography–tandem mass spectrometry following a supported liquid extraction (SLE) was developed. Serum and saliva samples of 0.2 mL were extracted by SLE three times using 0.4 mL of methyl tert-butyl ether each time. The chromatographic separation was obtained on an Agilent Poroshell column using a 0.01% formic acid buffer and acetonitrile (60:40, v/v) as the solvent with a flow rate of 0.3 mL/min. Optimized quantitative mass transitions for cortisol, cortisone, and cortisone d-4 were 363.2/121.0 (m/z), 361.2/163.1 (m/z), and 367.1/270.7 (m/z), respectively. The method validation was achieved according to regulatory guidance. The lower limit of quantification (LLOQ) in serum were 2 ng/mL for cortisol and 1 ng/mL for cortisone, and the LLOQ in saliva were 0.1 ng/mL for cortisol and 0.2 ng/mL for cortisone. The developed method showed convenient and efficient extraction, a lower LLOQ, and a short running time. Modest correlations between serum and saliva cortisol and cortisone concentrations were found. The method was successfully applied in assessing the HPA condition of patients with depressive disorders.
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Diederich, S., M. Quinkler, K. Miller, P. Heilmann, M. Schöneshöfer, and W. Oelkers. "Human kidney 11β-hydroxysteroid dehydrogenase: regulation by adrenocorticotropin?" European Journal of Endocrinology 134, no. 3 (March 1996): 301–7. http://dx.doi.org/10.1530/eje.0.1340301.

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Diederich S, Quinkler M, Miller K, Heilmann P, Schöneshöfer M, Oelkers W. Human kidney 11βhydroxysteroid dehydrogenase: regulation by adrenocorticotropin? Eur J Endocrinol 1996;134:301–7. ISSN 0804–4643 In ectopic adrenocorticotropin (ACTH) syndrome (EAS) with higher ACTH levels than in pituitary Cushing's syndrome and during ACTH infusion, the ratio of cortisol to cortisone in plasma and urine is increased, suggesting inhibition of renal 11β-hydroxysteroid dehydrogenase (11β-HSD) by ACTH or by ACTH-dependent steroids. Measuring the conversion of cortisol to cortisone by human kidney slices under different conditions, we tested the possibility of 11β-HSD regulation by ACTH and corticosteroids. Slices prepared from unaffected parts of kidneys removed because of renal cell carcinoma were incubated with unlabeled or labeled cortisol, and cortisol and cortisone were quantitated after HPLC separation by UV or radioactive detection. The 11β-HSD activity was not influenced by incubation with increasing concentrations (10−12–10−9 mol/l) of ACTH (1–24 or 1–39) for 1 h. Among 12 ACTH-dependent steroids tested (10−9–10−6 mol/l), only corticosterone (IC50 = 2 × 10−7 mol/l), 18-OH-corticosterone and 11βOH-androstenedione showed a significant dose-dependent inhibition of 11β-HSD activity. The percentage conversion rate of cortisol to cortisone was concentration dependent over the whole range of cortisol concentrations tested (10−8–10−5 mol/l). A direct inhibitory effect of ACTH on 11β-HSD is, therefore, unlikely. The only steroids inhibiting the conversion of cortisol to cortisone are natural substrates for 11β-HSD Kinetic studies show a saturation of the enzyme at high cortisol concentrations. Thus, the reduced percentage renal cortisol inactivation in EAS seems to be due mainly to overload of the enzyme with endogenous substrates (cortisol, corticosterone and others) rather than to direct inhibition of 11β-HSD by ACTH or ACTHdependent steroids, not being substrates of 11β-HSD. S Diederich, Department of Endocrinology, Klinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany
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Lee, Sanghoo, Hwan-Sub Lim, Hye-Jin Shin, Seol-A. Kim, Jimyeong Park, Hyun-Chul Kim, Hyogyeong Kim, et al. "Simultaneous Determination of Cortisol and Cortisone from Human Serum by Liquid Chromatography-Tandem Mass Spectrometry." Journal of Analytical Methods in Chemistry 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/787483.

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A fast, sensitive, and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was validated and then the levels of cortisol and cortisone from sera of healthy adults were determined by the LC-MS/MS method. One hundredμL of serum sample was directly extracted by adding 2 mL ethyl acetate, followed by chromatographic separation on a C18 column with a mobile phase consisting of 5 mM ammonium acetate and methanol (25 : 75, v/v). The precision, accuracy, and average recovery of the method were 1.5–5.3%, 95.4–102.5%, and 96.4% for cortisol, and 1.9–6.0%, 89.2–98.8%, and 79.9% for cortisone, respectively. The method was linear from 1.0 to 500.0 ng/mLr2=0.999for cortisol and 2.5 to 100.0 ng/mLr2=0.998for cortisone. The limits of detection (LOD) and quantification (LOQ) were 0.2 and 1.0 ng/mL for cortisol, and 1.0 and 2.5 ng/mL for cortisone, respectively. The average cortisol concentration (133.9±63.7 ng/mL) of samples collected between 9:00 and 11:00 a.m. was higher approximately 4.4 times than that of cortisone (30.5±10.7 ng/mL)P<0.0001. The average cortisone/cortisol ratio was 0.225. Therefore, the LC-MS/MS method may be useful for the diagnosis of some adrenal diseases and the assessment of 11β-hydroxysteroid dehydrogenase (11β-HSD) activity in clinical laboratories.
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Vieira, José Gilberto Henriques, Odete Hirata Nakamura, and Valdemir Melechko Carvalho. "Determination of cortisol and cortisone in human saliva by a liquid chromatography-tandem mass spectrometry method." Arquivos Brasileiros de Endocrinologia & Metabologia 58, no. 8 (November 2014): 844–50. http://dx.doi.org/10.1590/0004-2730000003347.

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Objective Salivary cortisol measurement plays an important role in the evaluation of adrenal function. Its high correlation with free serum cortisol, the easy of sampling and the limited presence of interfering steroids, generated multiple recent studies of its application, in special in the screening of adrenal hyperfunction. In this paper we present our experience in the development of a high pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for salivary cortisol and cortisone measurement. Materials and methods For this study we used 181 saliva samples from our routine diagnostic laboratory. The HPLC-MS/MS method was based on a Waters Quattro Premier tandem mass spectrometer with an electrospray probe. After derivatization with hydroxylamine transitions monitored included cortisol and cortisone. An in-house radioimmunoassay (RIA) was used for salivary cortisol results comparison. Results Functional sensitivity was 24 ng/dL for cortisol and linearity from 24 to 1929 ng/dL. Saliva cortisol values obtained in the 181 samples presented a median of 52 ng/dL with 5‐95% percentile of 24 and 374 ng/dL. With the RIA the results were 86, 25 and 436 ng/dL, respectively, with values for RIA being significantly higher (P<0.0001) and high correlation (r=0.8312, P<0.0001). Cortisone measured in 159 samples showed a median of 278 ng/dL, with 5‐95% percentile of 100 and 1,133 ng/dL. Correlation with cortisol values was significant (r=0.820, P<0.0001). Conclusion We conclude that the HPLC-MS/MS method compares favorably with the RIA for salivary cortisol measurement, with the additional possibility of concomitant cortisone measurement and the evaluation of 11βHSD2 activity.
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Kilgour, Alixe H. M., Scott Semple, Ian Marshall, Peter Andrews, Ruth Andrew, and Brian R. Walker. "11β-Hydroxysteroid Dehydrogenase Activity in the Brain Does Not Contribute to Systemic Interconversion of Cortisol and Cortisone in Healthy Men." Journal of Clinical Endocrinology & Metabolism 100, no. 2 (February 1, 2015): 483–89. http://dx.doi.org/10.1210/jc.2014-3277.

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Abstract Context and Objective: 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyses regeneration of cortisol in liver, adipose tissue, and skeletal muscle, making a substantial contribution to circulating cortisol as demonstrated in humans by combining stable isotope tracer infusion with arteriovenous sampling. In the brain, 11βHSD1 is a potential therapeutic target implicated in age-associated cognitive dysfunction. We aimed to quantify brain 11βHSD1 activity, both to assess its contribution to systemic cortisol/cortisone turnover and to develop a tool for measuring 11βHSD1 in dementia and following administration of 11βHSD1 inhibitors. Design, Setting, and Participants: With ethical approval and informed consent, 8 healthy men aged 38.1 years (sd 16.5) underwent an ECG-gated phase-contrast magnetic resonance scan to quantify internal jugular vein blood flow and were infused with 1,2 [2H]2-cortisone and 9,11,12,12 [2H]4-cortisol for 3 h before samples were obtained from the internal jugular vein and an arterialized hand vein. Steroids were quantified by liquid chromatography-tandem mass spectrometry. Main Outcome Measures and Results: Steady state tracer enrichments were achieved and systemic indices of cortisol/cortisone interconversion were consistent with previous studies in healthy men. However, there was no measurable release or production of cortisol, 9,12,12 [2H]3-cortisol or cortisone into the internal jugular vein. Conclusions: Although cerebral 11βHSD1 reductase activity may be greater in cognitively impaired patients, in healthy men any contribution of 11βHSD1 in the brain to systemic cortisol/cortisone turnover is negligible. The influence of 11βHSD1 in the brain is likely confined to subregions, notably the hippocampus. Alternative approaches are required to quantify pharmacodynamics effects of 11βHSD1 inhibitors in the human brain.
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Gambineri, Alessandra, Flaminia Fanelli, Federica Tomassoni, Alessandra Munarini, Uberto Pagotto, Ruth Andrew, Brian R. Walker, and Renato Pasquali. "Tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 in overweight/obese women with polycystic ovary syndrome compared with weight-matched controls." European Journal of Endocrinology 171, no. 1 (July 2014): 47–57. http://dx.doi.org/10.1530/eje-13-1030.

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ContextAbnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic–pituitary–adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity.ObjectiveTo assess cortisol clearance and whole-body and tissue-specific activities of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) in PCOS.DesignCase–control study.SettingMedical center.PatientsA total of 20 overweight–obese unmedicated Caucasian women with PCOS, aged 18–45 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, andHSD11B1genotypes (rs846910 and rs12086634).Main outcome measuresCortisol metabolites were measured in 24 h urine. During steady-state 9,11,12,12-[2H]4-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-2H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity andHSD11B1mRNA were measured,ex vivo, in biopsies.ResultsUrinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (P<0.05), whereas subcutaneous abdominal adipose tissueHSD11B1mRNA levels and activity were increased (P<0.05) in women with PCOS when compared with controls.ConclusionsTissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS.
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Abbas, Maha Jamal, Kahtan Adnan Abood, and Lehad M. Al Azzawi. "Salivary Cortisol Level Pre and Post MRI Scanning." Al Mustansiriyah Journal of Pharmaceutical Sciences 16, no. 2 (December 1, 2016): 53–61. http://dx.doi.org/10.32947/ajps.v16i2.110.

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The measurement of salivary cortisol level has become a reliable method for studying the adrenal cortical function and it is response to different intrinsic and extrinsic factors such as medications and stressful factors. The aims of this study is to investigate if there is difference between sex and the effect of time of testing on salivary cortisol level, pre and post was scanning, data for cortisol, Salivary Flow Rate (SFR) and PH of saliva were analyzed. Non-stimulated salivary samples from 24 subjects (8 males, 16 females) pre and post scanning with Magnetic resonance imaging (MRI) was collected and the diurnal variation was taken into consideration for that all the pre and post scanning samples collected at the morning. Salivary cortisol was measured by ELISA technique, PH of saliva was measured by PH meter and salivary flow rate by specific equation. The results shows there was significant difference in the level of salivary cortisol, SFR and PH of saliva pre and post examination and there was positive correlation with regard to cortisol level and PH of saliva pre and post scanning, just the salivary flow rate showed negative correlation, in addition the results revealed significant difference with regards to the sex of the participant as well as positive correlation between salivary PH and SFR in pretest phase and positive correlation between salivary cortisol level, SFR in post scanning phase. From the results of this study we can conclude that the exposure to MRI scanning have an effect on Hypothalamic pituitary –adrenal axes and predispose to significant changes in cortisol level post scanning and this difference must be taken into consideration in concern to effect of raising the level of cortisone on other variables.
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Schutter, D. J. L. G., J. van Honk, E. H. F. de Haan, A. C. van Huffelen, and H. P. F. Koppeschar. "Cortisol, depression and reduced cortico-cortical cross-talk in Cushing’s syndrome." Journal of Endocrinological Investigation 27, no. 7 (July 2004): 683–86. http://dx.doi.org/10.1007/bf03347504.

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Torday, J. S., M. Post, and B. T. Smith. "Compartmentalization of 11-oxidoreductase within fetal lung alveolus." American Journal of Physiology-Cell Physiology 249, no. 1 (July 1, 1985): C173—C176. http://dx.doi.org/10.1152/ajpcell.1985.249.1.c173.

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The role of 11-oxidoreductase in the cellular process of fetal lung surfactant production and its localization within the alveolar domain have been investigated. In organotypic cultures of fetal rat lung, cortisol and cortisone markedly stimulate saturated phosphatidylcholine synthesis by the alveolar type II cell; a 10-fold excess of 11-ketoprogesterone blocks the bioactivity of cortisone. Both cortisol and cortisone also stimulate fibroblast-pneumonocyte factor production, whereas 11-ketoprogesterone blocks the effect of cortisone, but not of cortisol, suggesting that cortisone stimulation of fibroblast-pneumonocyte factor production depends on its conversion to cortisol by 11-oxidoreductase. A survey of the cells that are present in the alveolar domain revealed that 11-oxidoreductase activity is only present in the fibroblast. Localization of both 11-oxidoreductase and fibroblast-pneumonocyte factor production within the same cell emphasizes the significance of 11-oxidoreductase in the regulation of fetal lung surfactant production.
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Ueland, Grethe Å., Paal Methlie, Ralf Kellmann, Marit Bjørgaas, Bjørn O. Åsvold, Ketil Thorstensen, Oskar Kelp, et al. "Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test." European Journal of Endocrinology 176, no. 6 (June 2017): 705–13. http://dx.doi.org/10.1530/eje-17-0078.

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ObjectivesThe overnight dexamethasone (DXM) suppression test (DST) has high sensitivity, but moderate specificity, for diagnosing hypercortisolism. We have evaluated if simultaneous measurement of S-DXM may correct for variable DXM bioavailability and increase the diagnostic performance of DST, and if saliva (sa) is a feasible adjunct or alternative to serum.Design and methodsProspective study of DST was carried out in patients with suspected Cushing’s syndrome (CS) (n = 49), incidentaloma (n = 152) and healthy controls (n = 101). Cortisol, cortisone and DXM were assayed by liquid chromatography–tandem mass spectrometry (LC–MS/MS).ResultsThree hundred and two subjects underwent DST; S-cortisol was ≥50 nmol/L in 83 patients, of whom 11 had CS and 27 had autonomous cortisol secretion. The lower 2.5 percentile of S-DXM in subjects with negative DST (n = 208) was 3.3 nmol/L, which was selected as the DXM cut-off level. Nine patients had the combination of low S-DXM and positive DST. Of these, three had been misdiagnosed as having autonomous cortisol secretion. DST results were highly reproducible and confirmed in a replication cohort (n = 58). Patients with overt CS had significantly elevated post-DST sa-cortisol and sa-cortisone levels compared with controls; 23 of 25 with autonomous cortisol secretion had elevated sa-cortisone and 14 had elevated sa-cortisol.ConclusionsSimultaneous measurement of serum DXM and cortisol reduced false-positive DSTs by 20% and improved the specificity. S-DXM >3.3 nmol/L is sufficient for the suppression of cortisol <50 nmol/L. Measurement of glucocorticoids in saliva is a non-invasive and easy procedure and post-DST sa-cortisone was found particularly useful in the diagnosis of CS.
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36

Wake, Deborah J., Natalie Z. M. Homer, Ruth Andrew, and Brian R. Walker. "Acute In Vivo Regulation of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity by Insulin and Intralipid Infusions in Humans." Journal of Clinical Endocrinology & Metabolism 91, no. 11 (November 1, 2006): 4682–88. http://dx.doi.org/10.1210/jc.2006-0819.

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Abstract Context: Extraadrenal regeneration of cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11HSD1) is increased after a mixed meal. It is unknown which tissue is responsible and whether this reflects the complex transcriptional control of 11HSD1 or posttranscriptional control exerted by supply of reduced nicotinamide adenine dinucleotide phosphate from hexose-6-phosphate dehydrogenase. Objective: The objective of this study was to test whether hyperinsulinemia and/or increased serum free fatty acids increase whole-body and intraadipose 11HSD1, and whether adipose 11HSD1 switches from dehydrogenase to reductase activity. Methods: In nine healthy men, we measured whole-body cortisol regeneration (by iv infusion of 9,11,12,12-[2H]4-cortisol) and intra-adipose interconversion of cortisol and cortisone (by sc microdialysis infusion of [3H]4-cortisol and [3H]2-cortisone in separate cannulae) during: 1) a hyperinsulinemic euglycemic clamp; 2) iv lipid infusion (Intralipid 20% fat emulsion); and 3) saline infusion, each for 3.5 h. Results: Hyperinsulinemia increased rate of appearance of 9,12,12-[2H]3-cortisol (19.3 ± 0.8 vs. 16.7 ± 1.1 nmol/min with saline, P &lt; 0.001), indicating increased whole-body 11HSD1. Within adipose, the predominant reaction was reductase conversion of cortisone to cortisol (after 3.5 h of saline infusion, reaching 11.0 ± 2.7% per hour reductase vs. 5.2 ± 1.3 dehydrogenase, P &lt; 0.02); insulin increased reductase (reaching 15.8 ± 3.0, P &lt; 0.05) and tended to increase dehydrogenase activity. Intralipid infusion had no effects on whole-body deuterated cortisol metabolism, but increased both dehydrogenase and reductase (reaching 16.7 ± 1.8, P &lt; 0.01) activities in adipose. Conclusions: Hyperinsulinemia and increased free fatty acids induce acute increases in 11HSD1 activity in adipose tissue that are not attributable to a switch from dehydrogenase to reductase. Hyperinsulinemia also increases systemic cortisol regeneration. These effects may enhance intracellular cortisol concentrations after a meal.
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37

Wade, Stephen E., and Albert D. Haegele. "Time-integrated measurement of corticosteroids in saliva by oral diffusion sink technology." Clinical Chemistry 37, no. 7 (July 1, 1991): 1166–72. http://dx.doi.org/10.1093/clinchem/37.7.1166.

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Abstract Saliva, as a medium for assessing adrenocortical function in humans, has many advantages and a few distinct disadvantages. Interpretation of measurements of saliva cortisol is complicated by the contamination of saliva by steroid-binding proteins from blood plasma, enzyme activity in the salivary gland that converts cortisol to cortisone, and the amplification in saliva of the episodic fluctuations in systemic cortisol concentrations. We describe a new measurement technology that rejects artifacts from contamination of saliva by plasma protein, provides for measurement of both cortisol and cortisone, and integrates episodic fluctuations in concentration over a period of hours. This oral diffusion sink technology may greatly enhance the reliable interpretation of corticosteroid concentrations measured in saliva.
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38

Izov, N., A. Alexandrova, L. Petrov, M. Kachaunov, T. Sheytanova, and S. Kolimechkov. "DYNAMICS OF TRAINING DISTRESS, PERFORMANCE, AND EXCRETION OF CORTISOL AND CORTISONE IN URINE DURING SIX WEEKS OF TRAINING IN ELITE SWIMMERS." Human Sport Medicine 20, S1 (October 16, 2020): 84–91. http://dx.doi.org/10.14529/hsm20s111.

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Aim. Optimal balance between training intensity and recovery is of particular importance for elite swimmers in order to improve their results. The aim of this study was to record the dyna­mics of training distress, performance, and excretion of cortisol and cortisone in urine during six weeks of training in elite swimmers. Materials and Methods. Twenty-four participants (10 women and 14 men) from the national swimming team of Bulgaria took part in this study, with an average age of 18.7 ± 3.78 years. Training distress (TDS) and urine concentration of cortisol and cortisone were evaluated every two weeks. In total, the measurements were taken on the 1-st (T1), 14-th (T2), 28-th (T3) and 42-nd days (T4). Anthropometric measurements were also taken at T1 and T4, and body fat percentage and muscle mass percentage were calculated by skinfold methods. Results. The TDS score at T4 (6.92 ±7.15) was significantly lower than this at T1 (14.96 ± 10.63) and T2 (15.21 ± 12.44). The concentrations of cortisol at T3 (35.9 ± 47.7) and T4 (35.0 ± 24.2) were also significantly lower than that registered at T1 (82.7 ± 62.8). The concentration of cortisone did not show any significant differences across T1 to T4, but the sum of cortisol and cortisone urine concentration was significantly lower in T3 and T4 vs T1. Conclusion. The significantly reduced cortisol concentration in urine in T4, as well as the sum of the concentrations of cortisol and cortisone, were in line with the reduction of the TDS score in T4.
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39

Johnstone, AM, P. Faber, R. Andrew, ER Gibney, M. Elia, G. Lobley, RJ Stubbs, and BR Walker. "Influence of short-term dietary weight loss on cortisol secretion and metabolism in obese men." European Journal of Endocrinology 150, no. 2 (February 1, 2004): 185–94. http://dx.doi.org/10.1530/eje.0.1500185.

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OBJECTIVES: Obesity is associated with increased inactivation of cortisol by hepatic A-ring 5alpha- and 5beta-reductases, impaired hepatic regeneration of cortisol from cortisone by 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), but increased subcutaneous adipose 11HSD1 activity enhancing local cortisol levels in fat. Cause and effect between obesity and abnormal cortisol metabolism is untested. DESIGN: Acute weight loss was induced by very low calorie diet (VLCD) or starvation in obese men. METHODS: Otherwise healthy males (aged 20-55 years; body mass index (BMI) 30-40 kg/m2) were studied after 6 days on a weight maintenance diet; then after either 6 days of starvation (n=6) or 3 weeks of VLCD (2.55 MJ; n=6); then after 1 week of weight maintenance; and finally after 2 weeks of being allowed to feed ad libitum. Plasma samples were obtained from indwelling cannulae at 0930 h and 1815 h and a 24 h urine collection was completed for analysis of cortisol metabolites by gas chromatography/mass spectrometry. RESULTS: Data are mean+/-S.E.M. BMI fell (kg/m3) from 34.8+/-0.8 at baseline to 31.8+/-1.4 on VLCD and 32.7+/-1.1 on starvation. Starvation caused a rise in plasma cortisol (at 0930 h from 143+/-17 to 216+/-11 nM, P<0.001) but no change in total urinary cortisol metabolites. VLCD did not alter plasma cortisol and markedly reduced cortisol metabolite excretion (from 15.8+/-1.1 mg/day at baseline to 7.0+/-1.1 mg/day, P<0.001). Relative excretion of 5alpha-reduced cortisol metabolites fell on both diets, but there were no changes in cortisol/cortisone metabolite ratios reflecting 11HSD activities. CONCLUSIONS: Weight loss with VLCD in obesity reverses up-regulation of hepatic A-ring reductases and normalises cortisol production rate; in contrast, starvation produces acute stress and further activation of cortisol secretion. We suggest that activation of cortisol secretion is not an irreversible intrinsic abnormality in obese patients, and speculate that dietary content has an important influence on the neuroendocrine response to weight loss.
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40

Wulansari, Dwi Putri, Lusi Epsilawati, Farina Pramanik, and Suhardjo Sitam. "The value of Mental Index (MI) and Gonial Index (GI) in hypertension patients on its correlation with serum calcium and cortisol level." Jurnal Radiologi Dentomaksilofasial Indonesia (JRDI) 5, no. 2 (August 31, 2021): 44. http://dx.doi.org/10.32793/jrdi.v5i2.688.

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Objective: This research was aimed to analyze the mandibular cortical width based on a mental index (MI) and gonial Index (GI) in hypertension patients correlated with serum calcium and cortisol levels. Materials and Methods: This study was an analytic-observational study with 31 hypertension patients aged 41-79. All of the patients have checked their serum calcium and cortisol level. The panoramic radiograph was taken and analyzed using Image-J Fiji software. The mandibular cortical width was then measured with Mental Index (MI) and Gonial Index (GI) and correlated with the serum calcium and cortisol level. Results: The data obtained from examining serum calcium and cortisol levels and the measurement of Mental Index (MI) and Gonial Index (GI) showed varying results but tended towards normal values. The results of the correlation test between mental index and gonial index with cortisol and serum calcium showed no correlation with p>0.05. Conclusion: There was no correlation between serum calcium and cortisol level in the value of MI and GI in hypertension patients.
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41

Quinkler, M., H. Troeger, E. Eigendorff, C. Maser-Gluth, A. Stiglic, W. Oelkers, V. Bahr, and S. Diederich. "Enhanced 11beta-hydroxysteroid dehydrogenase type 1 activity in stress adaptation in the guinea pig." Journal of Endocrinology 176, no. 2 (February 1, 2003): 185–92. http://dx.doi.org/10.1677/joe.0.1760185.

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The 11beta-hydroxysteroid dehydrogenases (11beta-HSDs) convert cortisol to its inactive metabolite cortisone and vice versa. 11beta-HSD type 1 (11beta-HSD-1) functions as a reductase in vivo, regulating intracellular cortisol levels and its access to the glucocorticoid receptor. In contrast, 11beta-HSD-2 only mediates oxidation of natural glucocorticoids, and protects the mineralocorticoid receptor from high cortisol concentrations. We investigated the in vivo and in vitro effects of ACTH on the recently characterized 11beta-HSDs in guinea pig liver and kidney. Tissue slices of untreated guinea pigs were incubated with (3)H-labelled cortisol or cortisone and ACTH(1-24) (10(-10) and 10(-9) mol/l). The 11beta-HSD activities in liver and kidney slices were not influenced by in vitro incubation with ACTH(1-24). In addition, guinea pigs were treated with ACTH(1-24) or saline injections s.c. for 3 days. Liver and kidney tissue slices of these animals were incubated with (3)H-labelled cortisol or cortisone. In vivo ACTH treatment significantly increased reductase and decreased oxidase activity in liver and kidney. Furthermore, 11beta-HSD-1 activity assessed by measurement of the urinary ratio of (tetrahydrocortisol (THF)+5alphaTHF)/(tetrahydrocortisone) was significantly increased after ACTH treatment compared with the control group. Plasma levels of cortisol, cortisone, progesterone, 17-hydroxyprogesterone and androstenedione increased significantly following in vivo ACTH treatment. The enhanced reductase activity of the hepatic and renal 11beta-HSD-1 is apparently caused by cortisol or other ACTH-dependent steroids rather than by ACTH itself. This may be an important fine regulation of the glucocorticoid tonus for stress adaptation in every organ, e.g. enhanced gluconeogenesis in liver.
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42

Hollanders, Jonneke J., Bibian van der Voorn, Noera Kieviet, Koert M. Dolman, Yolanda B. de Rijke, Erica L. T. van den Akker, Joost Rotteveel, Adriaan Honig, and Martijn J. J. Finken. "Interpretation of glucocorticoids in neonatal hair: a reflection of intrauterine glucocorticoid regulation?" Endocrine Connections 6, no. 8 (November 2017): 692–99. http://dx.doi.org/10.1530/ec-17-0179.

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Background Glucocorticoids (GCs) measured in neonatal hair might reflect intrauterine as well as postpartum GC regulation. We aimed to identify factors associated with neonatal hair GC levels in early life, and their correlation with maternal hair GCs. Methods In a single-center observational study, mother–infant pairs (n = 107) admitted for >72 h at the maternity ward of a general hospital were included. At birth and an outpatient visit (OPV, n = 72, 44 ± 11 days postpartum), maternal and neonatal hair was analyzed for cortisol and cortisone levels by LC–MS/MS. Data were analyzed regarding: (1) neonatal GC levels postpartum and at the OPV, (2) associations of neonatal GC levels with maternal GC levels and (3) with other perinatal factors. Results (1) Neonatal GC levels were >5 times higher than maternal levels, with a decrease in ±50% between birth and the OPV for cortisol. (2) Maternal and neonatal cortisol, but not cortisone, levels were correlated both at postpartum and at the OPV. (3) Gestational age was associated with neonatal GC postpartum (log-transformed β (95% CI): cortisol 0.07 (0.04–0.10); cortisone 0.04 (0.01–0.06)) and at the OPV (cortisol 0.08 (0.04–0.12); cortisone 0.00 (−0.04 to 0.04)), while weaker associations were found between neonatal GCs and other perinatal and maternal factors. Conclusions Neonatal hair GCs mainly reflect the third trimester increase in cortisol, which might be caused by the positive feedback loop, a placenta-driven phenomenon, represented by the positive association with GA. Between birth and 1.5 months postpartum, neonatal hair cortisol concentrations decrease sharply, but still appear to reflect both intra- and extrauterine periods.
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43

Quinkler, Marcus, and Paul M. Stewart. "Hypertension and the Cortisol-Cortisone Shuttle." Journal of Clinical Endocrinology & Metabolism 88, no. 6 (June 2003): 2384–92. http://dx.doi.org/10.1210/jc.2003-030138.

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Stewart, Paul M., and Christopher R. W. Edwards. "The cortisol-cortisone shuttle and hypertension." Journal of Steroid Biochemistry and Molecular Biology 40, no. 4-6 (January 1991): 501–9. http://dx.doi.org/10.1016/0960-0760(91)90269-b.

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45

Stewart, Paul M., and J. Ian Mason. "Cortisol to cortisone: Glucocorticoid to mineralocorticoid." Steroids 60, no. 1 (January 1995): 143–46. http://dx.doi.org/10.1016/0039-128x(94)00024-7.

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46

SAPSE, A. "Cortisol, high cortisol diseases and anti-cortisol therapy." Psychoneuroendocrinology 22 (1997): S3—S10. http://dx.doi.org/10.1016/s0306-4530(97)00024-3.

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47

Sharp, Victoria, Lisa M. Thurston, Robert C. Fowkes, and Anthony E. Michael. "11β-Hydroxysteroid dehydrogenase enzymes in the testis and male reproductive tract of the boar (Sus scrofa domestica) indicate local roles for glucocorticoids in male reproductive physiology." Reproduction 134, no. 3 (September 2007): 473–82. http://dx.doi.org/10.1530/rep-07-0126.

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11β-Hydroxysteroid dehydrogenase (11βHSD) enzymes modulate the target cell actions of corticosteroids by catalysing metabolism of the physiological glucocorticoid (GC), cortisol, to inert cortisone. Recent studies have implicated GCs in boar sperm apoptosis. Hence, the objective of this study was to characterise 11βHSD enzyme expression and activities in the boar testis and reproductive tract. Although 11βHSD1 and 11βHSD2 mRNA transcripts and proteins were co-expressed in all tissues, cortisol–cortisone interconversion was undetectable in the corpus and cauda epididymides, vas deferens, vesicular and prostate glands, irrespective of nucleotide cofactors. In contrast, homogenates of boar testis, caput epididymidis and bulbourethral gland all displayed pronounced 11βHSD activities in the presence of NADPH/NADP+ and NAD+, and the penile urethra exhibited NAD+-dependent 11β-dehydrogenase activity. In kinetic studies, homogenates of boar testis, caput epididymidis and bulbourethral gland oxidised cortisol with Km values of 237–443 and 154–226 nmol/l in the presence of NADP+ and NAD+ respectively. Maximal rates of NADP+-dependent cortisol oxidation were 7.4- to 28.5-fold greater than the Vmax for NADPH- dependent reduction of cortisone, but were comparable with the rates of NAD+-dependent cortisol metabolism. The relatively low Km estimates for NADP+ -dependent cortisol oxidation suggest that either the affinity of 11βHSD1 has been increased or the cortisol inactivation is catalysed by a novel NADP+-dependent 11βHSD enzyme in these tissues. We conclude that in the boar testis, caput epididymidis and bulbourethral gland, NADP+- and NAD+-dependent 11βHSD enzymes catalyse net inactivation of cortisol, consistent with a physiological role in limiting any local actions of GCs within these reproductive tissues.
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48

White, Perrin C. "Alterations of Cortisol Metabolism in Human Disorders." Hormone Research in Paediatrics 89, no. 5 (2018): 320–30. http://dx.doi.org/10.1159/000485508.

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The interconversion of active and inactive corticosteroids – cortisol and cortisone, respectively, in humans – is modulated by isozymes of 11β-hydroxysteroid dehydrogenase (11-HSD). Studies of this process have provided crucial insights into glucocorticoid effects in a wide variety of tissues. The 11-HSD1 isozyme functions mainly as an oxoreductase (cortisone to cortisol) and is expressed at high levels in the liver and other glucocorticoid target tissues. Because it is required for full physiological effects of cortisol, it has emerged as a drug target for metabolic syndrome and type 2 diabetes. Mutations in the corresponding HSD11B1 gene, or in the H6PD gene encoding hexose-6-phosphate dehydrogenase (which supplies the NADPH required for the oxoreductase activity of 11-HSD1), cause apparent cortisone reductase deficiency, a rare syndrome of adrenocortical hyperactivity and hyperandrogenism. In contrast, the 11-HSD2 isozyme functions as a dehydrogenase (cortisol to cortisone) and is expressed mainly in mineralocorticoid target tissues, where it bars access of cortisol to the mineralocorticoid receptor. Mutations in the HSD11B2 gene encoding 11-HSD2 cause the syndrome of apparent mineralocorticoid excess, a severe form of familial hypertension. The role of this enzyme in the pathogenesis of common forms of low-renin hypertension remains uncertain.
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49

Jnanendrappa, K. H. "A Study on Correlation between Serum Cortisol and Stroke Severity with Serum Cortisol." Academia Journal of Medicine 2, no. 2 (July 24, 2019): 179–81. http://dx.doi.org/10.21276/ajm.2019.2.2.46.

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50

Jahangard, Leila, Thorsten Mikoteit, Saman Bahiraei, Mehrangiz Zamanibonab, Mohammad Haghighi, Dena Sadeghi Bahmani, and Serge Brand. "Prenatal and Postnatal Hair Steroid Levels Predict Post-Partum Depression 12 Weeks after Delivery." Journal of Clinical Medicine 8, no. 9 (August 23, 2019): 1290. http://dx.doi.org/10.3390/jcm8091290.

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Background: Within three to six months after delivery, 13%–19% of women suffer from post-partum depression (PPD), understood as a dysfunctional adaptation to the postpartum condition and motherhood. In the present cross-sectional study, we compared the hair steroid levels of women 12 weeks before and after delivery and with or without PPD. Method: The present study was a cross-sectional study conducted twelve weeks after delivery. At that time, 48 women (mean age: 25.9 years) with PPD and 50 healthy controls (mean age: 25.2 years) completed questionnaires on depressive symptoms. Further, at the same time point, 6 cm lengths of hair strands were taken, providing samples of hair steroids 12 weeks before and 12 weeks after delivery in order to analyze hair steroids (cortisol, cortisone, progesterone, testosterone, and dehydroepiandrosterone (DHEA)). Results: Compared to those of women without PPD, hair steroid levels (cortisol, cortisone, progesterone) were significantly lower in women with PPD both before and after delivery. Lower prenatal cortisone and progesterone levels predicted higher depression scores 12 weeks after delivery. Lower prenatal levels of cortisol and progesterone and higher levels of DHEA, and postnatal lower levels of cortisol, cortisone, and progesterone, along with higher levels of DHEA predicted PPD-status with an accuracy of 98%. Conclusions: PPD is associated with blunted hair cortisol, cortisone, and progesterone secretions both pre- and postpartum. Such blunted steroid levels appear to reflect a stress responsivity that is less adaptive to acute and transient stressors. It follows that prenatally assessed low hair cortisol and progesterone levels, along with high DHEA levels, are reliable biomarkers of post-partum depression 12 weeks after delivery.
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