Journal of Clinical Endocrinology & Metabolism, Vol 54, 145-149, Copyright © 1982 by Endocrine Society

ARTICLES

Decreased glucocorticoid receptor binding in adrenal insufficiency

JA Schlechte and BM Sherman

To examine the effect of glucocorticoid deficiency on the glucocorticoid receptor, we examine the binding of [3H] dexamethasone to lymphocytes in normal subjects and patients with adrenal insufficiency before and after glucocorticoid replacement therapy. Using a whole cell competitive binding assay, normal human lymphocytes had 5977 +/- 1487 (mean +/- SD) binding sites/cell and a dissociation constant of 10 +/- 2 nM. Lymphocytes from patients with untreated adrenal insufficiency had fewer binding sites (3364 +/-322) and a 2- fold increase in binding affinity (5.4 +/- 0.9 mM). The administration of conventional replacement doses of cortisone acetate for 6 months caused no change in receptor number, but was associated with a decrease in binding affinity toward normal. After long term glucocorticoid replacement therapy, binding parameters were similar to those in patients before treatment. The physiological implications of the decreased receptor number and increased binding affinity in adrenal insufficiency remain to be elucidated.

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