Lymphocyte glucocorticoid receptor binding in depressed patients with hypercortisolemia.
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.
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*
D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D006854:Hydrocortisone