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Clinical Chemistry 42: 249-254, 1996;
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Clinical Chemistry, Vol 42, 249-254, Copyright © 1996 by American Association for Clinical Chemistry

Effect of cortisol on percentage of non-sex-hormone-bound steroid: implications for distribution of steroids on binding proteins in serum

RR Cooke, JE McIntosh and RP Murray-McIntosh
Department of Obstetrics and Gynaecology, Wellington School of Medicine, New Zealand.

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.


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H. Dechaud, A. Denuziere, S. Rinaldi, J. Bocquet, H. Lejeune, and M. Pugeat
Age-Associated Discrepancy between Measured and Calculated Bioavailable Testosterone in Men
Clin. Chem., April 1, 2007; 53(4): 723 - 728.
[Abstract] [Full Text] [PDF]


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