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 language | English (US) |
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Pages (from-to) | 151-167 |
Number of pages | 17 |
Journal | Psychoneuroendocrinology |
Volume | 25 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2000 |
Externally published | Yes |
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