Influence of dexamethasone on peripheral metabolic parameters of cortisol in the adult male conscious guinea-pig.

The influence of dexamethasone on distribution, metabolism and protein binding of cortisol was studied in conscious adult male guinea-pigs, under chronic cannulation, by a single injection technique for cortisol metabolic parameters and Sephadex equilibrium dialysis procedure for protein binding. The results showed that biological half-life of cortisol (51-55 min) was identical in control and in dexamethasone-treated guinea-pigs (low plasma cortisol level). The apparent volume of distribution of cortisol, which was higher in control (550 +/- 20 ml) than in dexamethasone-treated animals (380 +/- 30 ml), was related to the higher plasma cortisol level in controls (0.96 +/- 0.07 mumole/l) as compared to dexamethasone-treated animals (0.12 +/- 0.02 mole/l). When a high cortisol concentration was infused in dexamethasone-treated guinea-pigs in order to produce hig plasma cortisol level, plasma cortisol MCR increased by 80% (P less than 0.001) reflecting increases of 50% (P less than 0.001) in the apparent volume of distribution and decreases of 19% (0.01 less than P less 0.02) in the half-life cortisol compared to dexamethasone-treated animals (low plasma cortisol level). Although the plasma cortisol level was higher (P less than 0.001) in dexamethasone-treated animals infused with non-labelled cortisol (2.9 +/- 0.02 mumol/l) than in controls (0.96 +/- 0.07 mumol/l), the identical values of the apparent volume of distribution in dexamethasone-treated animals infused with non-labelled cortisol and in controls suggested that dexamethasone could alter the distribution of cortisol, and therefore its metabolism. Dexamethasone did not modify the transcortin-binding capacity and did not complete with cortisol on transcortin sites in guinea-pig plasma.