title: Normal pituitary response to metyrapone in the morning in depressed patients: implications for circadian regulation of corticotropin-releasing hormone secretion.
abstract: Excess secretion of cortisol in depressed patients has been documented by a number of investigators, which is presumed secondary to increased corticotropin (ACTH) and ACTH-releasing hormone (CRH) secretion. To unmask the proposed increased central (CRH) drive, we administered metyrapone in the AM to 13 depressed and 13 age- and sex-matched normal control subjects. Metyrapone administration resulted in a prompt decrease in plasma cortisol and in an increase in 11-deoxycortisol, the inactive precursor, in all subjects. Both depressed patients and normal control subjects demonstrated clear increases in ACTH and beta-lipotropin/beta-endorphin production. There were no significant differences between patients and controls in any hormonal measures following metyrapone administration. These data suggest that: 1) in the absence of negative feedback (cortisol blockade), mildly to moderately depressed outpatients do not manifest increased central drive in the morning; and 2) the secretory capacity of the corticotropes do not differ between such depressed patients and controls.
authors.affiliation: Mental Health Research Institute, University of Michigan, Ann Arbor 48109, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Young
authors.forename: J F
authors.initials: JF
authors.lastname: Lopez
authors.forename: V
authors.initials: V
authors.lastname: Murphy-Weinberg
authors.forename: S J
authors.initials: SJ
authors.lastname: Watson
authors.forename: H
authors.initials: H
authors.lastname: Akil
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000097:blood*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008797:Metyrapone / Q000627:therapeutic use*; D010902:Pituitary Gland / Q000187:drug effects*; D001615:beta-Endorphin / Q000097:blood
chemical_list: D006728:Hormones; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone; D008797:Metyrapone