INTERSPECIES VARIATIONS OF CORTICOSTEROID-BINDING GLOBULIN PARAMETERS

In mammalian plasma, cortisol binds to a specific alpha(1)-glycoprotei n: corticosteroid-binding globulin (CBG). In this study, we measured t he protein binding of cortisol by equilibrium dialysis in seven specie s in which plasma cortisol concentrations varied from 0.02 to 0.05 (ew e, dog, cow) to 0.1 to 0.6 (horse, human, cynomolgus monkey) to reach 1.6 mu M (squirrel monkey). No binding of cortisol to CBG was discerni ble in plasma from squirrel monkey. In all other species examined, we showed that the CBG maximal capacity (B-max) was 3 (1.7 to 5.2) times more than the plasma cortisol levels, with cow, dog, ewe exhibiting th e lowest and cynomolgus monkey exhibiting the highest values. We also noted the existence of a linear relationship between B-max and the cor responding dissociation constant (K-d), B-max being systematically 10 (8.5 to 11.8) times more than K-d. The low binding affinity of cortiso l assigned to albumin did not differ between species. The free (6 to 1 4%), CBG-bound (67 to 87%), and albumin-bound (7 to 19%) cortisol frac tions calculated from the estimated binding parameters and measured pl asma cortisol concentrations were similar within species, except for s quirrel monkey, in which half of the cortisol was albumin bound, and t he other half remained protein free. Our most appealing finding was th at in most species, as much as 68% of plasma CBG remained free of cort isol under physiologic conditions. These results are discussed with re spect to the theories concerning the role of CBG in plasma transport a nd the local delivery of cortisol and free CBG as a proper hormone.