Dexamethasone suppression of corticosteroid secretion: Evaluation of the site of action by receptor measures and functional studies

Michael A. Cole, Paul J. Kim, Brian A. Kalman, Robert L. Spencer

Research output: Contribution to journalArticle

165 Scopus citations

Abstract

A dose of dexamethasone was determined in rats (50 μg/kg SC) that suppressed the corticosterone response to restraint stress by 80%. Corticosteroid receptor occupancy estimates found that the 50 μg/kg SC dose of dexamethasone had no significant effect on available glucocorticoid receptor (GR) or mineralococrticoid receptor (MR) binding in brain regions (hypothalamus, hippocampus and cortex); on the other hand dexamethasone produced a selective and significant decrease in available GR in peripheral tissues (pituitary and spleen). Functional studies showed that the 50 μg/kg SC dose of dexamethasone completely blocked the effects of corticotropin-releasing hormone (CRH; 0.3-3.0 μg/kg IP) on corticosterone secretion, but did not inhibit the corticosterone response to an adrenocorticotropin hormone (ACTH; 2.5 I.U./kg IP) challenge. These studies indicate that this dose of dexamethasone exerts its inhibitory effects on the HPA axis primarily by acting at GR in the pituitary. The plasma dexamethasone levels produced by this dose of dexamethasone are similar to those present in humans the afternoon after an oral dexamethasone suppression test (DST), a time at which many depressed patients escape from dexamethasone suppression. These results support and extend other studies which suggest that the DST provides a direct test of the effects of increased GR activation in the pituitary on ACTH and cortisol secretion. Copyright (C) 1999 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)151-167
Number of pages17
JournalPsychoneuroendocrinology
Volume25
Issue number2
DOIs
StatePublished - Feb 2000
Externally publishedYes

Keywords

  • Corticosteroid receptors
  • Corticosterone
  • HPA axis
  • Hippocampus
  • Pituitary
  • Rats

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

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