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

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 42; no. 2; pp. 249 - 254
• Main Authors: Cooke, RR, McIntosh, JE, Murray-McIntosh, RP
• Format: Journal Article
• Language: English
• Published: Washington, DC Am Assoc Clin Chem 01.02.1996; American Association for Clinical Chemistry
• Subjects: Analytical, structural and metabolic biochemistry; Binding, Competitive; Biological and medical sciences; Circadian Rhythm; Computer Simulation; Dexamethasone - pharmacology; Estradiol - blood; Female; Fundamental and applied biological sciences. Psychology; Humans; Hydrocortisone - blood; Hydrocortisone - pharmacology; Male; Other biological molecules; Progesterone - pharmacology; Protein Binding; Sex Hormone-Binding Globulin - metabolism; Terpenes, steroids. Hormones; Testosterone - blood; Transcortin - metabolism; Human; Biological fluid; Ligand binding; Androgen; Steroid hormone; Cortisol; Glucocorticoid; In vitro; Binding protein; Testosterone; Binding capacity; Adrenal hormone; Serum; Testicular hormone; Sex steroid hormone
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1093/clinchem/42.2.249

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.