EFFECT OF CORTISOL ON PERCENTAGE OF NON-SEX-HORMONE-BOUND STEROID - IMPLICATIONS FOR DISTRIBUTION OF STEROIDS ON BINDING-PROTEINS IN SERUM

We previously observed that in men concentrations of serum testosteron e (T) not bound to sex-hormone-binding globulin (n-SHBGT) decreased as concentrations of cortisol increased in early morning. This led us to investigate in vitro the influence of several steroids on protein-bou nd T. Steroids were added to late-evening sera containing low concentr ations of cortisol, Changes were measured in percent T or estradiol no t bound to SHBG (%n-SHBGT or %n-SHBGE), Results were compared with com puter simulations of a mass action model describing current understand ing of steroid binding to serum proteins. In vitro measurements confir med changes observed in vivo, Cortisol at 600 nmol/L reduced %n-SHBGT to 61% +/- 5% of basal, but this was reversed with cortisol at 2000 nm ol/L. Progesterone reduced %n-SHBGT less, and dexamethasone had no eff ect. Free T rose with added cortisol. Increasing estradiol to 900 nmol /L caused an increase in %n-SHBGT. The %n-SHBGE rose with added cortis ol (121% +/- 5% of basal with cortisol at 1000 mmol/L). Simulation pre dicted all behaviors except the marked initial decrease in %n-SHBGT as cortisol concentrations increased and the absolute values of %n-SHBGT and %n-SHBGE. A possible explanation for the former is that T is disp laced from corticosteroid-binding globulin (CBG) by added cortisol, mo re T is bound to CBG than expected, and T displaced from CBG associate s with SHBG rather than albumin, Alternatively, current understanding about steroid binding to serum proteins has other major deficiencies.