Erythrocyte-associated cortisol: measurement, kinetics of dissociation, and potential physiological significance.

It is well known that a portion of the cortisol in blood is associated with erythrocytes. This study was conducted to determine the quantity of cortisol associated with erythrocytes under physiological conditions and to assess the potential availability of that cortisol for tissue uptake. The erythrocyte-associated cortisol was determined from the volume of plasma measured using [125I]human serum albumin, the concentration of cortisol in plasma, and the total concentration of cortisol in blood. The plasma unbound cortisol fraction was determined by ultrafiltration and was used to calculate a partitioning coefficient that describes the distribution of cortisol between erythrocyte-associated and plasma unbound components. The cortisol partitioning coefficient (erythrocyte-associated cortisol concentration divided by plasma unbound cortisol concentration) did not vary significantly over a wide range of cortisol levels, nor was it affected by the presence or absence of corticosteroid-binding globulin. The cortisol partitioning coefficient in six normal men averaged 2.62 +/- 0.16 (mean +/- SD). Computer analysis of the distribution of cortisol among blood components indicated that at all cortisol levels, the proportion of blood cortisol associated with erythrocytes would exceed that which is plasma unbound or albumin-bound. The rate of dissociation of cortisol from erythrocytes was measured to determine if the kinetics of dissociation would be consistent with the tissue availability of erythrocyte-associated cortisol. Indeed, the half-time of dissociation was extremely rapid (less than 2.3 s). These results indicate that erythrocyte-associated cortisol is a substantial component of blood cortisol and that erythrocytes may serve as a major conduit for the transport of cortisol to the tissues.