Temperature-Dependent Cortisol Distribution among the Blood Compartments in Man
Abstract
This study was conducted to investigate the effect of temperature on the amount of cortisol bound to the erythrocytes and the distribution of cortisol in whole blood at various temperatures. The amount of cortisol bound to the erythrocytes was determined in a way that did not disturb the equilibrium distribution of cortisol between plasma and erythrocytes. Total and free cortisol concentrations in plasma and the amount of cortisol bound to the erythrocytes were determined at 20, 30, 37, and 40 C in the blood of six healthy persons. The amount of cortisol bound to the erythrocytes showed a perfect linear relation with the free cortisol concentration and was independent from the temperature. The average ratio of the erythrocyte-associated and free cortisol was 2.38 +/- 0.06. Computer simulations of the distribution of cortisol among the blood compartments showed that the free and loosely bound fraction (albumin and erythrocytes) was highly temperature dependent: at 30 C, this fraction was 3-5 times lower than at 37 C. It was demonstrated by computer simulation that changes in the concentration of cortisol-binding globulin had an effect on the fractional distribution of cortisol among the blood components. These shifts in the cortisol distribution, between the erythrocyte and the plasma compartment, can also be the cause of apparently high or low free and total plasma cortisol concentrations. Differences up to 25% in the free cortisol concentration can be observed. We conclude that the erythrocyte-associated cortisol fraction is relatively undervalued but can serve as an important transport vehiculum and storage compartment for cortisol. This fraction can have a considerable effect on the total plasma and free cortisol concentration when strict temperature control during sample handling is not considered.
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Lentjes and Romijn published data from which free unbound cortisol could be calculated.
“Lentjes and Romijn published Data from which free unbound cortisol could be calculated [2].”
From Bioavailability of Oral Hydrocortisone Corrected for Binding Proteins and Measured by LC-MS/MS Using Serum Cortisol and Salivary Cortisone (2018) · cites this paper as [2]
Unbound serum cortisol was estimated using published data [2] rather than measured directly.
“Serum cortisol was corrected for saturable binding using published data [2] to give an estimate of unbound serum cortisol (note in the design of the original study no plans were made to measure unbound plasma cortisol).”
From Bioavailability of Oral Hydrocortisone Corrected for Binding Proteins and Measured by LC-MS/MS Using Serum Cortisol and Salivary Cortisone (2018) · cites this paper as [2]
Individual total serum cortisol concentration-time data were used to calculate the unbound cortisol profiles based on a literature derived model, and errors introduced here may have contributed to the higher variability seen in the data.
“One limitation of the current study is that individual total serum cortisol concentration-time data were used to calculate the unbound cortisol profiles based on a literature derived model, errors introduced here may have contributed to the higher variability seen in the data.”
From Bioavailability of Oral Hydrocortisone Corrected for Binding Proteins and Measured by LC-MS/MS Using Serum Cortisol and Salivary Cortisone (2018) · cites this paper as [2]
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Whitaker, M. J., Spielmann, S., Digweed, D., Huatan, H., Eckland, D., Johnson, T. N., Tucker, G., Krude, H., Blankenstein, O., & Ross, R. J. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-4060 · Cited by 48 · see citing works
Bancos, I., Erickson, D., Bryant, S., Hines, J., Nippoldt, T. B., Natt, N., & Singh, R. (2015) · Endocrine Practice · doi:10.4158/ep15820.or · Cited by 19 · see citing works
Melin, J., Parra-Guillen, Z. P., Hartung, N., Huisinga, W., Ross, R. J., Whitaker, M. J., & Kloft, C. (2018) · Clinical Pharmacokinetics · doi:10.1007/s40262-017-0575-8 · Cited by 17 · see citing works
TN, J., MJ, W., B, K., & RJ, R. (2018) · Journal of Bioequivalence & Bioavailability · doi:10.4172/jbb.1000365 · Cited by 12 · see citing works
“CBG has high affinity for cortisol but lower capacity whereas albumin has a lower affinity and higher capacity and Lentjes and Romijn published Data from which free unbound cortisol could be calculated [2].”
Method
- Authors
- Lentjes, E. G. W. M., & Romijn, F. H. T. P. M.
- Affiliations
- Leiden University Medical Center (NL)
- ORCID
- Lentjes, E. G. W. M.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1999-02
- Volume
- 84
- Issue
- 2
- Pages
- 682-687
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2136962727
- Cited by
- 29
- References
- 0
- Citations by year
- 2026: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2015: 5 · 2014: 1 · 2012: 1
- FWCI
- 0.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- cortisol, free cortisol, corticosteroid-binding globulin, temperature dependence, plasma cortisol, sample handling, computer simulation
- MeSH terms
- Adult, Carrier Proteins, Computer Simulation, Erythrocytes, Humans, Hydrocortisone, Male, Plasma, Protein Binding, Reference Values, Serum Albumin, Temperature
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