Context: Interindividual variation and tissue specificity of glucocorticoid (GC) sensitivity may occur in healthy subjects.

Objective and Participants: To evaluate the GC sensitivity in 40 healthy young subjects (21F, 19M; 22-42 yr old).

Design: We measured salivary and plasma cortisol levels pre- and post 0.25, 0.5 and 1 mg of DEX given at 11:00p.m. We also evaluated the pattern of dexamethasone (DEX)-mediated inhibition of concanavalin-A -stimulated peripheral blood mononuclear cell (PBMC) proliferation using different DEX doses and the number of binding sites (Bmax) and the affinity of glucocorticoid receptor (Kd).

Results: The increasing DEX doses resulted in a dose-dependent decrease of cortisol levels. The majority of the subjects (70%) suppressed cortisol with DEX doses lower than 0.5 mg and two did not suppress even with 1 mg of DEX. The Bmax was 4.1 ± 0.3 fmol/mg protein and the Kd was 8.1 ± 1.3 nM. Four individuals presented elevated Kd. PBMC proliferation was inhibited by DEX in a dose-dependent pattern. The median IC₅₀ value was 7.1 x 10^-7 mol/L. We found 77.5% (31/40) concordance among all three tests; 29 subjects showed all parameters between percentile 10 and 90 (P10-P90), one above P90, and one below P10. These two subjects could be classified as more glucocorticoid -resistant or -sensitive, respectively. No concordance between in vivo and in vitro tests in two subjects suggested a tissue specific sensitivity.

Conclusions: This is the first report that, taking advantages of three bioassays performed on the same subject, demonstrated a considerable interindividual variability and tissue specific GC sensitivity in a young healthy population.