Corticosteroid receptor expression and in vivo glucocorticoid sensitivity in multiple sclerosis

• mRNA from 58 MS patients´ peripheral blood was compared to that from 18 controls.
• Glucocorticoid (GR) and mineralocorticoid receptor expression was lower in MS.
• GILZ, DUSP1 and FKBP5, genes activated by GR, displayed higher expression in MS.
• With higher disability, GR and MR decreased; GR target expression was bell-shaped.
• Decreased GR expression is probably compensated by hypercortisolemia, shown earlier.

To estimate the efficiency of glucocorticoid signaling in multiple sclerosis in vivo, we measured mRNA expression of glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and four genes regulated by GR and implicated in immune function, in whole blood. GR expression and MR expression were significantly lower in 52 patients than in 18 controls. In contrast, expression of GR regulated genes was increased (significantly for glucocorticoid induced leucine zipper, GILZ), especially in mildly impaired patients. Reduced GR expression appears to be compensated, either by hyperactive hypothalamo–pituitary–adrenal axis or by intracellular adaptations.