Down regulation of glucocorticoid receptors in early-diagnosed rheumatoid arthritis

In patients with rheumatoid arthritis (RA) of longer duration, glucocorticoid receptor (GR) down-regulation has been reported without any change in cortisol levels. This phenomenon might play a role in the aetio-pathogenesis of RA. Therefore we studied GR expression, as well as the serum cortisol levels, in patients with recently diagnosed RA.

In 81 early diagnosed RA patients with disease duration < 1 year (52F/29M; mean (SD) age 63 (13) years) and in 39 age and sex matched controls (23F/16M; mean age 63 (15) years) blood samples were taken between 8-10 h AM. GR expression (GR-number and GR-affinity), serum cortisol levels, ESR, CRP, painful and swollen joints were measured.

A significantly lower GR-number was found in the female patients compared with female controls: 7.0 versus 9.8fmol/million cells, respectively (difference: 2.8, 95% CI 1.1 - 4.6). Interestingly, also serum cortisol levels were significantly lower in the female patients compared with the female controls: 0.21 versus 0.41 micromol/l, respectively (difference: 0.20, 95% CI 0.12 - 0.28). However, between the male patients and male controls no difference was found in GR expression nor in serum cortisol levels. Neither in female nor in male patients were correlations found between GR expression and parameters of disease activity nor was there a relation between GR expression and serum cortisol levels.

Changes in GR expression as well as serum cortisol were not a general phenomenon in early diagnosed RA patients, being present only in females and not related to disease activity. Therefore it seems unlikely that GR expression per se is causally involved in the pathogenesis of RA. We cannot preclude that it may be involved in the incidence, severity and course of RA, as this may be differentially regulated in males and females.