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Glucocorticoid Sensitivity in Young Healthy Individuals: in Vitro and in Vivo Studies

Departments of Internal Medicine (R.S.C., I.M.d.S., J.G.H.V., A.C.M., M.d.C.) and Physiology (L.L.K.E.), School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil

Address all correspondence and requests for reprints to: Dr. Margaret de Castro, School of Medicine of Ribeirao Preto, University of Sao Paulo, Avenida dos Bandeirantes 3900, 14049-900, Ribeirao Preto, Sao Paulo, Brazil. E-mail: castrom{at}fmrp.usp.br.

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

Objective and Participants: The objective of this study was to evaluate the GC sensitivity in 40 healthy young subjects (21 women and 19 men; 22–42 yr old).

Design: We measured salivary and plasma cortisol levels before and after the administration of 0.25, 0.5, and 1 mg dexamethasone (DEX), given at 2300 h. We also evaluated the pattern of DEX-mediated inhibition of concanavalin A-stimulated peripheral blood mononuclear cell proliferation using different DEX doses, the number of binding sites, and the affinity of the GC receptor (K_d).

Results: The increasing DEX doses resulted in a dose-dependent decrease in 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 DEX. The binding capacity was 4.1 ± 0.3 fmol/mg protein, and the K_d was 8.1 ± 1.3 nM. Four individuals presented with elevated K_d. Peripheral blood mononuclear cell proliferation was inhibited by DEX in a dose-dependent pattern. The median IC₅₀ value was 7.1 x 10^–7 mol/liter. We found 77.5% (31 of 40) concordance among all three tests; 29 subjects showed all parameters between the 10th and 90th percentiles (P10-P90), one above P90, and one below P10. These two subjects could be classified as more GC 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 advantage of three bioassays performed on the same subject, demonstrated a considerable interindividual variability and tissue-specific GC sensitivity in a young healthy population.

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