Binding characteristics of the glucocorticoid receptor in peripheral bloodlymphocytes in multiple sclerosis

Although the exact etiology of multiple sclerosis (MS) remains unresolved, immune reactions are believed to be the central pathogenic mechanisms. Endo genous and therapeutic steroid hormones affect the immune system, and infla mmatory diseases are associated with activation of the hypothalamic-pituita ry-adrenal axis, providing evidence of an immune-endocrine interplay. Funct ion tests in MS have revealed dysregulation of the hypothalamic-pituitary-a drenal system in a substantial proportion of patients. We characterized glu cocorticoid receptor (GR) binding in peripheral blood lymphocytes from 39 M S patients and 14 age- and sex-matched controls with respect to dissociatio n constant and binding capacity, using a whole-cell binding assay with [H-3 ]dexamethasone as the ligand. GR binding parameters did not differ signific antly between patients (K-d 8.98 +/- 1.07 nM, B-max 183 +/- 29.8 fmol/mg) a nd controls (K-d 9.36 +/- 1.17 nM, B-max 158 +/- 16 fmol/mg). No effect of age, sex, course, duration or severity of disease, or prior steroid treatme nts was detected. GR binding parameters were analyzed in relation to the re sults of the combined dexamethasone-CRH test, which reflects corticosteroid receptor function at the hypothalamus, in 30 patients and 9 controls. Whil e controls showed a moderate correlation between binding affinity of the GR in lymphocytes and regulatory function at the hypothalamic level, the pati ents did not. These data suggest that the physiological relationship betwee n binding and function of the glucocorticoid receptor is disturbed in MS.