Effect of temperature on protein binding of cortisol

Objectives: Biological effects of cortisol are substantially determined by protein binding of the hormone. The aim of our study was to characterize temperature effects on cortisol protein binding by use of an equilibrium dialysis method. Design and methods: Serum samples obtained from ten healthy volunteers were submitted to equilibrium dialysis. Each sample from the individuals was incubated for 16 h at 37 °C, 38 °C, 39 °C, 40 °C and 41 °C, respectively. In the dialysate samples obtained, cortisol concentrations were measured by immunoassay. Results: For samples incubated at 37 °C, a mean dialysate cortisol concentration of 0.41 μg/dL (SD = 0.14) was found. Gradual increase of dialysate cortisol concentration was observed with increasing incubation temperatures. For samples incubated at 41 °C, a mean dialysate cortisol of 0.75 μg/dL (SD = 0.24) was found. Thus, the mean percentage of free-to-total cortisol increased by about 80% from 3.7% (SD = 1.1) at 37 °C to 6.7% (SD = 1.8) at 41 °C. Conclusions: The results of our in vitro experiments suggest that during fever the free-to-total ratio of cortisol is increased substantially compared to normal conditions, and that administration of antipyretic drugs might potentially be associated with substantial changes in the bioavailability of cortisol.