Binding characteristics of the glucocorticoid receptor in peripheral blood lymphocytes in multiple sclerosis

Abstract

Although the exact etiology of multiple sclerosis (MS) remains unresolved, immune reactions are believed to be the central pathogenic mechanisms. Endogenous and therapeutic steroid hormones affect the immune system, and inflammatory diseases are associated with activation of the hypothalamic-pituitary-adrenal axis, providing evidence of an immune-endocrine interplay. Function tests in MS have revealed dysregulation of the hypothalamic-pituitary-adrenal system in a substantial proportion of patients. We characterized glucocorticoid receptor (GR) binding in peripheral blood lymphocytes from 39 MS patients and 14 age- and sex-matched controls with respect to dissociation constant and binding capacity, using a whole-cell binding assay with [3H]dexamethasone as the ligand. GR binding parameters did not differ significantly between patients (Kd 8.98 +/- 1.07 nM, Bmax 183 +/- 29.8 fmol/mg) and controls (Kd 9.36 +/- 1.17 nM, Bmax 158 +/- 16 fmol/mg). No effect of age, sex, course, duration or severity of disease, or prior steroid treatments was detected. GR binding parameters were analyzed in relation to the results of the combined dexamethasone-CRH test, which reflects corticosteroid receptor function at the hypothalamus, in 30 patients and 9 controls. While controls showed a moderate correlation between binding affinity of the GR in lymphocytes and regulatory function at the hypothalamic level, the patients did not. These data suggest that the physiological relationship between binding and function of the glucocorticoid receptor is disturbed in MS.

A Randomized Trial Comparing the Efficacy and Safety of Intravitreal Triamcinolone With Standard Care to Treat Vision Loss Associated With Macular Edema Secondary to Branch Retinal Vein Occlusion

“…The 4-mg dose was evaluated because it was the one used most commonly in clinical practice when the SCORE Study was initiated. The 1-mg dose was evaluated because this dose is likely to exceed the concentration necessary to saturate the glucocorticoid receptors in the cell cytoplasm 44,45. In addition, it was anticipated that, compared with the 4-mg dose, the 1-mg dose would have a lower risk of steroid-related adverse events.…”

A Randomized Trial Comparing the Efficacy and Safety of Intravitreal Triamcinolone With Observation to Treat Vision Loss Associated With Macular Edema Secondary to Central Retinal Vein Occlusion

“…The 1-mg dose was evaluated because this dose is likely to exceed the concentration necessary to saturate the glucocorticoid receptors in the cell cytoplasm 37,38. In addition, it was anticipated that, compared with the 4-mg dose, the 1-mg dose would have a lower risk of steroid-related adverse events.…”

A Randomized Trial Comparing Intravitreal Triamcinolone Acetonide and Focal/Grid Photocoagulation for Diabetic Macular Edema

“…The 1 mg dose was included because this dose was likely to exceed the concentration necessary to saturate the glucocorticoid receptors in the cell cytoplasm completely 51, 52. Also, it was hoped that adverse effects on the lens and intraocular pressure might be less frequent.…”