title: Disturbed glucocorticoid receptor autoregulation and corticotropin response to dexamethasone in depressives pretreated with metyrapone.
abstract: We studied glucocorticoid receptor autoregulation and corticotropin response to dexamethasone in depressed patients and controls, attempting to control for the confounding effect of endogenous glucocorticoids. After depletion of endogenous cortisol, depressed patients showed an attenuated suppressibility of corticotropin by dexamethasone in the face of unchanged dexamethasone plasma levels. Beta-endorphin levels were strongly correlated with adrenocorticotropic hormone (ACTH) concentrations. Although metyrapone administration resulted in a marked rise of glucocorticoid receptor sites per cell in controls, this effect was not present in depressives. These data support the hypothesis of a decreased glucocorticoid receptor plasticity and a partial steroid resistance in depression.
authors.affiliation: Department of Psychiatry, University of Würzburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Rupprecht
authors.forename: J
authors.initials: J
authors.lastname: Kornhuber
authors.forename: N
authors.initials: N
authors.lastname: Wodarz
authors.forename: J
authors.initials: J
authors.lastname: Lugauer
authors.forename: C
authors.initials: C
authors.lastname: Göbel
authors.forename: D
authors.initials: D
authors.lastname: Haack
authors.forename: G
authors.initials: G
authors.lastname: Beck
authors.forename: O A
authors.initials: OA
authors.lastname: Müller
authors.forename: P
authors.initials: P
authors.lastname: Riederer
authors.forename: H
authors.initials: H
authors.lastname: Beckmann
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000097:blood* / Q000175:diagnosis / Q000523:psychology; D003866:Depressive Disorder / Q000097:blood* / Q000175:diagnosis / Q000523:psychology; D003907:Dexamethasone / Q000493:pharmacokinetics; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008797:Metyrapone; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D011292:Premedication; D011569:Psychiatric Status Rating Scales; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000502:physiology; D001615:beta-Endorphin / Q000097:blood
chemical_list: D011965:Receptors, Glucocorticoid; D001615:beta-Endorphin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D008797:Metyrapone