Protein Binding of Cortisol in Human Cerebrospinal Fluid

A method devised previously to precisely measure the concentration of unbound cortisol was used to compare plasma and cerebrospinal fluid (CSF) in 34 patients. In CSF the percentage of free cortisol was 88.4 +/- 6.3% (mean +/- SD). Its concentration was 4.94 +/- 2.00 ng/ml, only one third of the concentration of unbound cortisol in plasma of the same patients (14.3 +/- 8.8 ng/ml). Total and unbound cortisol in CSF were correlated with unbound cortisol in plasma; however, this correlation was rather loose (r = 0.527 and 0.554, respectively) due to large individual variations. Moreover, at high concentrations of unbound cortisol in plasma, the ratio of total cortisol in CSF/unbound cortisol in plasma was decreased. Thus, it is impossible to simply consider cortisol in CSF as a dialyzate of cortisol in plasma. The binding of cortisol in CSF was due to a protein having the electrophoretic mobility in polyacrylamide gels of plasma corticosteroid-binding globulin (CBG), and displaying the same hormonal specificity. The concentration of this protein was measured in 16 individual patients. This concentration, when expressed per protein content, was about two thirds of that of plasma CBG, and this ratio was extremely variable in individual patients. Individual variations of cortisol-binding globulin in CSF could not be attributed to variations of CBG in plasma nor to variations of protein content in CSF. There was an inverse relationship (r = 0.888) between unbound cortisol in CSF and the concentration of cortisol-binding globulin in this fluid, showing that CBG exerts a physiological role in CSF.