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Submitted on January 12, 2005
Accepted on August 2, 2005
Department of Internal Medicine and Department of Physiology - School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil
* To whom correspondence should be addressed. 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: 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.
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