Interrelations between binding affinity and metabolic clearance rate for the main corticosteroids in the rabbit.

In the rabbit, the metabolic clearance rate (MCR) was found to be higher for corticosterone than for cortisol. At the same time corticosterone, aldosterone and 11-dehydrocorticosterone showed similar MCR while cortisone ranged at intermediate levels between cortisol and corticosterone. The relative binding affinity of transcortin to the corticosteroids, as calculated by an in vitro technique, decreased progressively from cortisol, to cortisone, then to corticosterone, then 11-dehydrocorticosterone and, finally to aldosterone. The occurrence of antibodies in plasma, induced against aldosterone, corticosterone or even cortisone resulted in a marked decrease in the MCR of the corresponding steroid, to the level measured in controls for cortisol. We deduced that, in rabbits: (1) the MCR of a corticosteroid is clearly connected with its binding to a specific protein; (2) in spite of the relatively high binding affinity of transcortin for corticosterone as compared to other species it nevertheless appears unable to significantly protect the steroid against peripheral metabolism; (3) a very effective protection is however, induced, by raising a specific antibody with a high binding affinity for corticosterone.