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 testosterone (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-bound T. Steroids were added to late-evening sera containing low concentrations of cortisol. Changes were measured in percent T or estradiol not bound to SHBG (%n-SHBGT or %n-SHBGE). Results were compared with computer simulations of a mass action model describing current understanding of steroid binding to serum proteins. In vitro measurements confirmed 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 nmol/L. Progesterone reduced %n-SHGBT less, and dexamethasone had no effect. Free T rose with added cortisol. Increasing estradiol to 900 nmol/L caused an increase in %n-SHBGT. The %n-SHBGE rose with added cortisol (121% +/- 5% of basal with cortisol at 1000 nmol/L). Simulation predicted 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 displaced from corticosteroid-binding globulin (CBG) by added cortisol, more T is bound to CBG than expected, and T displaced from CBG associates with SHBG rather than albumin. Alternatively, current understanding about steroid binding to serum proteins has other major deficiencies.
Cooke
R R
RR
Department of Obstetrics and Gynaecology, Wellington School of Medicine, New Zealand.
McIntosh
J E
JE
Murray-McIntosh
R P
RP
D001667:Binding, Competitive; D002940:Circadian Rhythm; D003198:Computer Simulation; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000494:pharmacology; D008297:Male; D011374:Progesterone / Q000494:pharmacology; D011485:Protein Binding; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013739:Testosterone / Q000097:blood*; D014156:Transcortin / Q000378:metabolism
D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D014156:Transcortin; D006854:Hydrocortisone