Glucocorticoid receptors in adrenocorticoid disorders

Circulating human lymphocytes contain glucocorticoid receptors (GR). To see if adrenocortical imbalance is associated with changes in the level of GR, several patients with hypo- and hypercortisolism were studied. Peripheral lymphocytes were prepared by Ficoll-Hypaque gradients and were then subjected to a whole cell-binding assay measuring the total cellular receptor pool, with [3H]dexamethasone as the ligand. There were no significant differences in the cellular content of GR among healthy controls, 10 patients with Cushing's syndrome, and 3 patients suffering from Addison's disease; the absolute levels of GR were 4850 +/- 1340, 4900 +/- 2160, and 5640 +/- 1110 (mean +/- SD) receptors/cell, respectively. The mean equilibrium dissociation constants of the interaction of [3H]dexamethasone with the receptor were also about the same in the 3 groups (1-2 X 10(-8) M). Thus, aberrations in glucocorticoid balance strong enough to produce clear-cut clinical symptoms do not result in major alterations in the level of the peripheral GR. We also studied an additional patient who had hypercortisolism due to an adrenal adenoma but only slight clinical signs of hypercortisolism; interestingly, her cellular GR level was only 30% of normal. The lymphocytic GR content was also below normal in 2 patients with anorexia nervosa.