Interindividual Glucocorticoid Sensitivity in Young Healthy Subjects: The Role of Glucocorticoid Receptor α and β Isoforms Ratio

Abstract

Only few studies have addressed the interindividual variation and tissue specificity of glucocorticoid (GC) sensitivity in healthy individuals, a phenomenon observed in pathological conditions. Alternative splicing of the glucocorticoid receptor (GR) produces α and β isoforms. GRβ has dominant-negative effects on hormone-induced GRα effects, and an increased expression of the GRβ has been associated with glucocorticoid resistance. We determined, using a simple, rapid, and accurate Real-Time PCR assay, the individual mRNAs expression of GRα and GRβ in 26 normal subjects (mean±SE, age 30±6 years; 12 males and 14 females), in order to evaluate the role of these isoforms in glucocorticoid sensitivity in health. Glyceraldehydes-3-phosphate dehydrogenase (GAPDH) was used as a housekeeper gene. GRα/GAPDH, GRβ/GAPDH and GRα/GRβ ratios showed a normal distribution. We observed a higher expression of GRα compared to GRβ and an interindividual variability in the GRα, GRβ, and GAPDH gene expressions in the young healthy population. In addition, no correlation was observed between GRα/GRβ ratio and the dexamethasone (DEX) doses needed to suppress plasma cortisol, GRα/GRβ ratio and the concentration of DEX that caused inhibition of Con-A stimulated cell proliferation, and GRα/GRβ ratio and the affinity of GR (K_d) of each subject. Therefore, the variability of GC sensitivity observed in normal subjects can not be ascribed to the variation in the GRα and GRβ expression.

Key words

Glucocorticoid receptor α and β isoforms - glucocorticoid sensitivity - real time PCR

References

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