Mononuclear leukocyte glucocorticoid receptor binding characteristics and down-regulation in major depression

A. Wassef, E. M. Smith, R. M. Rose, R. Gardner, H. Nguyen, Walter Meyer

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Some patients with major depressive disorder (MDD) have elevated plasma cortisol centrations and show failure to suppress cortisol secretion upon administration of dexamethasone (DEX), yet they do not have Cushingoid features. To study whether this represents glucocorticoid (GC) resistance, [3H]-DEX-binding assays were used to measure, in vitro, the GC receptor affinity (1/Kd) and number (Bmax) in mononuclear leukocytes of 11 MDD patients and 15 control subjects. No receptor abnormalities were detected in the MDD group; thus any cellular defect leading to a lack of responsiveness to GC in the MDD patients, if present, probably lies beyond the initial receptor binding. DEX (1.0 mg orally) was administered to study in vivo GC receptor down-regulation. Compared to the control group, fewer depressed subjects down-regulated Bmax after DEX. By paired t-test, Bmax decreased significantly in the control group but not in the depressed group. Receptor number on the control day did not correlate significantly with the degree of receptor down-regulation, severity of depression or cortisol concentrations across all the subjects. These results do not lend support to previous reports suggesting that GC resistance in MDD results from a GC receptor-binding abnormality, and they emphasize the importance of considering receptor studies in the context of GC-mediated cell processes in order to identify the exact cellular defect(s) leading to GC resistance.

Original languageEnglish (US)
Pages (from-to)59-68
Number of pages10
JournalPsychoneuroendocrinology
Volume15
Issue number1
DOIs
StatePublished - 1990

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Mononuclear Leukocytes
Glucocorticoid Receptors
Major Depressive Disorder
Down-Regulation
Dexamethasone
Depression
Hydrocortisone
Glucocorticoids
Control Groups
Glucocorticoid Receptor Deficiency

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Endocrine and Autonomic Systems
  • Psychology(all)

Cite this

Mononuclear leukocyte glucocorticoid receptor binding characteristics and down-regulation in major depression. / Wassef, A.; Smith, E. M.; Rose, R. M.; Gardner, R.; Nguyen, H.; Meyer, Walter.

In: Psychoneuroendocrinology, Vol. 15, No. 1, 1990, p. 59-68.

Research output: Contribution to journalArticle

Wassef, A. ; Smith, E. M. ; Rose, R. M. ; Gardner, R. ; Nguyen, H. ; Meyer, Walter. / Mononuclear leukocyte glucocorticoid receptor binding characteristics and down-regulation in major depression. In: Psychoneuroendocrinology. 1990 ; Vol. 15, No. 1. pp. 59-68.
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