Gm. Bright, CORTICOSTEROID-BINDING GLOBULIN INFLUENCES KINETIC-PARAMETERS OF PLASMA-CORTISOL TRANSPORT AND CLEARANCE, The Journal of clinical endocrinology and metabolism, 80(3), 1995, pp. 770-775
In an accompanying study, we reported a very poor correlation between
the magnitude of a continuous cortisol infusion in dexamethasone-suppr
essed adults and the resultant steady state plasma cortisol concentrat
ion (r(2) = 0.13). The concentration of corticosteroid-binding globuli
n (CBG) was found to explain an additional 39% of the variance in cort
isol response. We hypothesized that CBG might act by altering kinetic
parameters of cortisol transport. Accordingly, the rate of cortisol di
sappearance (K-d), volume of distribution (V), and pool size (P) were
determined after bolus injection of a stable isotope of cortisol in tw
o groups of healthy female subjects with both normal and elevated CBG
concentrations. The bolus studies were performed during continuous cor
tisol infusion and steady state conditions of plasma cortisol concentr
ation Two models were used to generate the kinetic parameters. The kin
etic parameters thus generated were able to predict the known cortisol
infusion rate with 4-16% error. The goodness of fit of modeled to exp
erimental data was excellent in all cases (>0.93). In both models, K-d
had a negative correlation to the CBG concentration (P < 0.05), a neg
ative correlation to the volume of distribution (P < 0.03), and a posi
tive correlation (P < 0.03) to pool size. Excellent correlations were
noted between both models in estimates of kinetic parameters (r(2) = 0
.82-0.97; P < 0.01). We conclude that CBG, in addition to its role of
transport protein, plays an active role in determining the disposition
of cortisol in humans.