title: Lymphocyte glucocorticoid receptor binding in depressed patients with hypercortisolemia.
abstract: Despite elevated levels of serum and urinary cortisol, patients with depressive illness manifest none of the clinical stigmata of glucocorticoid excess. This hypercortisolemia in the absence of clinical effects suggests a state of hormone resistance and could be mediated by alterations in the glucocorticoid receptor. Earlier studies have shown that small doses of glucocorticoids cause a decrease in glucocorticoid receptor binding in normal human lymphocytes. White cells from depressed patients with significant hypercortisolemia would be expected to show a similar change in receptor concentration if peripheral tissues are adequately exposed to and sensitive to the hormone. In this study we compared the binding of [3H]dexamethasone to lymphocytes from normal subjects and depressed patients with hypercortisolemia. Lymphocytes from normal subjects had a mean receptor concentration of 10.2 +/- 0.66 fm/10(6) cells (S.E.M.) and a dissociation constant of 4.8 +/- 0.47 nM. Lymphocytes from depressed patients with abnormal 0800 h serum cortisol after dexamethasone had a mean receptor concentration of 8.8 +/- 0.75 fm/10(6) cells, which was not significantly different from that in lymphocytes from normal subjects or from depressed subjects with normal post-dexamethasone cortisol levels (9.4 +/- 0.95 fm/10(6) cells). Lymphocytes from depressed patients with elevated urinary free cortisol excretion (UFC) also had normal receptor concentration and binding affinity for dexamethasone. The lack of a change in lymphocyte glucocorticoid receptor concentration in the presence of cortisol excess suggests the possibility that hypercortisolemia in depressive illness represents a state of peripheral glucocorticoid resistance.
mesh_terms: D000328:Adult; D003866:Depressive Disorder / Q000378:metabolism* / Q000503:physiopathology; D003907:Dexamethasone / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008214:Lymphocytes / Q000032:analysis*; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011965:Receptors, Glucocorticoid / Q000032:analysis*
chemical_list: D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D006854:Hydrocortisone