Adrenocorticotropin inhibition by restoration of normal evening cortisol levels

A measure of putative hippocampus-mediated glucocorticoid feedback in humans

Morris B. Goldman*, Gordon John Wood

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Hippocampus-mediated glucocorticoid negative feedback is thought to be relevant to the pathophysiology of neuropsychiatric disorders, but no reliable method of measuring it in humans has been developed. Converging lines of evidence indicate that basal hypothalamic-pituitary-adrenal axis activity during the unstressed circadian trough is primarily regulated by this feedback process. To assess whether negative feedback can be demonstrated under these circumstances, we studied normal controls (n = 5) who were pretreated with metyrapone to lower their basal evening cortisol levels. On two separate occasions, in double-blind randomized order, subjects received an infusion of cortisol or of saline. Restoration of normal evening plasma cortisol by the cortisol infusion produced a drop in plasma adrenocorticotropin (ACTH) apparent in the last sample obtained at +200 min (p < 0.05). The ACTH response in schizophrenic patients (n = 4), whose mental illness may arise from hippocampal dysfunction, was relatively blunted compared to that seen in normals (p < 0.02). 11-Desoxycortisol levels paralleled the ACTH responses across conditions and subject groups. These preliminary data suggest that hippocampus-mediated glucocorticoid feedback can be measured in normal subjects and may provide an index of hippocampal dysfunction in neuropsychiatric patients. Copyright (C) 2000 S. Karger AG, Basel.

Original languageEnglish (US)
Pages (from-to)396-401
Number of pages6
JournalNeuroendocrinology
Volume71
Issue number6
DOIs
StatePublished - Jan 1 2000

Fingerprint

Adrenocorticotropic Hormone
Glucocorticoids
Hydrocortisone
Hippocampus
Cortodoxone
Metyrapone

Keywords

  • Adrenal steroids
  • Clinical neuroendocrinology
  • Corticotropin
  • Hippocampus
  • Metyrapone
  • Schizophrenia

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

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abstract = "Hippocampus-mediated glucocorticoid negative feedback is thought to be relevant to the pathophysiology of neuropsychiatric disorders, but no reliable method of measuring it in humans has been developed. Converging lines of evidence indicate that basal hypothalamic-pituitary-adrenal axis activity during the unstressed circadian trough is primarily regulated by this feedback process. To assess whether negative feedback can be demonstrated under these circumstances, we studied normal controls (n = 5) who were pretreated with metyrapone to lower their basal evening cortisol levels. On two separate occasions, in double-blind randomized order, subjects received an infusion of cortisol or of saline. Restoration of normal evening plasma cortisol by the cortisol infusion produced a drop in plasma adrenocorticotropin (ACTH) apparent in the last sample obtained at +200 min (p < 0.05). The ACTH response in schizophrenic patients (n = 4), whose mental illness may arise from hippocampal dysfunction, was relatively blunted compared to that seen in normals (p < 0.02). 11-Desoxycortisol levels paralleled the ACTH responses across conditions and subject groups. These preliminary data suggest that hippocampus-mediated glucocorticoid feedback can be measured in normal subjects and may provide an index of hippocampal dysfunction in neuropsychiatric patients. Copyright (C) 2000 S. Karger AG, Basel.",
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