THE RATE CONSTANTS FOR THE INTERACTION OF CORTISOL AND TRANSCORTIN, AND THE RATE OF DISSOCIATION OF TRANSCORTIN-BOUND CORTISOL IN THE LIVER

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Abstract
SUMMARY: The apparent rate of dissociation of transcortin-bound cortisol in human plasma was measured. After establishing equilibrium between plasma proteins and endogenous and added [3H]cortisol, this was perturbed by addition of a known amount of exogenous cortisol. Plasma protein-bound [3H]cortisol was then measured by gel filtration at timed intervals. This system can be described by six differential equations, one each for unbound, albumin-bound and transcortin-bound cortisol and [3H]cortisol. The rate constants for the transcortin—cortisol reaction were estimated by numerical solution of these equations, using arbitrary rate constants for the albumin—steroid reaction. At 2 °C the dissociation of transcortin-bound cortisol has a rate constant of 0·00041 s−1, at 10 °C 0·00179 s−1 and at 22 °C 0·0353 s−1. At 37 °C the reaction was very rapid and equilibrium appeared to be attained in less than 5 s. The rate constant could only be estimated by using the Arrhenius equation, In (k) = const + E/RT, and was found to be 0·633 s−1. The rate constants for cortisol—plasma protein interaction were applied to a differential equation model for the splanchnic uptake of cortisol. Using experimental measurements of the visceral and hepatic uptake of cortisol in sheep the rate constant for the visceral removal of cortisol was found to be 0·0299 ± 0·0065 (s.e.m.) s−1 and the hepatic constant was 0·4674 ± 0·0540 (s.e.m.) s−1. In normal conscious sheep the total splanchnic uptake of cortisol appeared to be derived 42% from unbound, 31% from albumin-bound and 27% from transcortin-bound steroid.

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