The simultaneous measurement of cortisol with its downstream metabolites in human eccrine sweat is a sensitive approach to capture minute-to-minute stress responses. This study investigates exercise stress induced time dependent dynamic changes in cortisol, cortisone and downstream
inactive cortisol metabolites in human eccrine sweat using a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Cortisol and metabolite production (change in concentration over time) was measured in sweat at different time points during an administered exercise stress session with four healthy volunteers. Biomarker production plots were found to be highly individualized and sensitive to stress interventions such as exercise, and corresponded with stress response measures such as increases in heart rate. The LC-MS/MS method yielded baseline resolution between cortisol and cortisol metabolites with lower levels of detection and quantitation for each compound below 1 partper-billion (ppb). Cortisol and cortisol metabolites were found at concentrations ranging from 1 – 25 ppb in human eccrine sweat. They were also found to be stable in sweat with respect to temperature (37 C for up to 5 hours), pH (3-9) and freeze/thaw cycles (up to 4) This indicates that changes in these biomarker concentrations and their rate of production are due to stress-related physiological enzyme activation, rather than passive degradation in sweat. The physiological status of enzyme activation is thus captured and preserved in human eccrine sweat samples. This is advantageous for the development of wearable devices and methodologies which can assess human health, stress, wellbeing and performance.
Human Eccrine Sweat, Cortisol, Cortisone, Stress response, Resiliency, Sweat Gland, HPA axis
Bouslimani, A., Porto, C., Rath, C.M., Wang, M., Guo, Y., Gonzalez, A., Berg-Lyon, D., Ackermann, G., Christensen, G.J.M, Nakatsuji, T., Zhang, L.,
Borkowski, A.W., Meehan, M.J., Dorrestein, K., Gallo, R.L., Bandeira, N., Knight, R., Alexandrov, T., Dorrestein, P.C., 2015. Molecular cartography of the
human skin surface in 3D. Proc. Natl. Acad. Sci. 112, E2120–E2129. https://doi.org/10.1073/pnas.1424409112
Calderón-Santiago, M., Priego-Capote, F., Jurado-Gámez, B., Luque de Castro, M.D., 2014. Optimization study for metabolomics analysis of human sweat by liquid chromatography–tandem mass spectrometry in high resolution mode. J. Chromatogr. A 1333, 70–78. https://doi.org/https://doi.org/10.1016/j.chroma.2014.01.071
Calderón-Santiago, M., Priego-Capote, F., Turck, N., Robin, X., Jurado-Gámez, B., Sanchez, J.C., Luque de Castro, M.D., 2015. Human sweat metabolomics for lung cancer screening. Anal. Bioanal. Chem. 407, 5381–5392. https://doi.org/10.1007/s00216-015-8700-8
Chapman, K., Holmes, M., Seckl, J., 2013. 11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action. Physiol.
Rev. 93 (3), 1139–1206. https://doi.org/10.1152/physrev.00020.2012
Delgado-Povedano, M.M., Calderón-Santiago, M., Luque de Castro, M.D., Priego-Capote, F., 2018. Metabolomics analysis of human sweat collected after moderate exercise. Talanta 177, 47–65. https://doi.org/https://doi.org/10.1016/j.talanta.2017.09.028
Dodds, H.M., Taylor, P.J., Cannell, G.R., Pond, S.M., 1997. A High-Performance Liquid Chromatography – Electrospray – Tandem Mass Spectrometry Analysis of Cortisol and Metabolites in Placental Perfusate. Anal. Biochem. 347, 342–347.
Dodds, H.M., Taylor, P.J., Johnson, L.P., Mortimer, R.H., Pond, S.M., Cannell, G.R., 1997. Cortisol metabolism and its inhibition by glycyrrhetinic acid in the isolated perfused human placental lobule. J. Steroid Biochem. Mol. Biol. 62, 337–343. https://doi.org/10.1016/S0960-0760(97)00039-3
Csosz, É., Emri, G., Kallo, G., Tsaprailis, G., Toszer, J. 2015. Highly abundant defense proteins in human sweat as revealed by targeted proteomics and label-free quantification mass spectrometry. J. Eur. Acad. Dermatology Venereol. 29, 2024–2031. https://doi.org/10.1111/jdv.13221
Eisenschmid, B., Heilmann, P., Oelkers, W., Rejaibi, R., Schöneshöfer, M., 1987. 20-Dihydroisomers of cortisol and cortisone in human urine: excretion rates under different physiological conditions. J. Clin. Chem. Clin. Biochem. 25, 345–349.
Gambhir, S.S., Ge, T.J., Vermesh, O., Spitler, R., 2018. Toward achieving precision health. Sci. Transl. Med. 10.
Hughes, K.A., Manolopoulos, K.N., Iqbal, J., Cruden, N.L., Stimson, R.H., Reynolds, R.M., Newby, D.E., Andrew, R., Karpe, F., Walker, B.R., 2012. Recycling between cortisol and cortisone in human splanchnic, subcutaneous adipose, and skeletal muscle tissues in vivo. Diabetes 61, 1357–1364. https://doi.org/10.2337/db11-1345
Jia, M., Chew, W., Feinstein, Y., Skeath, P., Sternberg, E., 2016. Quantification of Cortisol in Human Eccrine Sweat by Liquid Chromatography - Tandem Mass Spectrometry. Analyst. https://doi.org/10.1039/C5AN02387D
Lee, A.L., Ogle, W.O., Sapolsky, R.M. 2002. Stress and depression: possible links to neuron death in the hippocampus. Bipolar Disord. 4, 117–128.
Murphy, D., West, H.F., 1969. Catabolism and interconversion of cortisol and cortisone in human synovial tissue in vitro. Ann. Rheum. Dis. 28, 637-643.
Peña, C.J., Monk, C., Champagne, F.A., 2012. Epigenetic effects of Prenatal stress on 11β-Hydroxysteroid Dehydrogenase-2 in the Placenta and fetal brain. PLoS One 7, e39791. https://doi.org/10.1371/journal.pone.0039791
Walker, B.R., Andrew. R. 2006. Tissue Production of Cortisol by 11β-Hydroxysteroid Dehydrogenase Type 1 and Metabolic Disease. Ann. N. Y. Acad. Sci. 1083, 165–184. https://doi.org/10.1196/annals.1367.012
Raiszadeh, M.M., Ross, M.M., Russo, P.S., Schaepper, M.A., Zhou, W., Deng, J., Ng, D., Dickson, A., Dickson, C., Strom, M., Osorio, C., Soeprono, T., Wulfkuhle, J.D., Petricoin, E.F., Liotta, L.A., Kirsch, W.M., 2012. Proteomic analysis of eccrine sweat: Implications for the discovery of schizophrenia biomarker proteins. J. Proteome Res. 11, 2127–2139. https://doi.org/10.1021/pr2007957
Rajan, V., Edwards, C.R., Seckl, J.R., 1996. 11 beta-Hydroxysteroid dehydrogenase in cultured hippocampal cells reactivates inert 11-
dehydrocorticosterone, potentiating neurotoxicity. J. Neurosci. 16, 65-70.
Sapolsky, R.M., Krey, L.C., McEwen, B.S., 1985. Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J. Neurosci. 5, 1222–1227. https://doi.org/10.1016/j.cmet.2007.09.011
Schöneshöfer, M., Weber, B., Nigam, S., 1983. Increased urinary excretion of free 20 alpha- and 20 betadihydrocortisol in a hypercortisolemic but
hypocortisoluric patient with Cushing's disease. Clin. Chem. 29, 385-389.
Thayer, J., Sternberg, E.M., 2006. Beyond Heart Rate Variability: Vagal Regulation of Allostatic Systems. Ann. N.Y. Acad. Sci 1088, 361–72.