Glucocorticoid receptors in depression

C. M. Pariante, C. B. Nemeroff, A. H. Miller

Research output: Contribution to journalReview article

44 Scopus citations

Abstract

During major depression, dysfunction of limbic structures resulting in hypersecretion of corticotropin-releasing factor (CRF) is believed to cause the well-known hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in this disorder. Nonsuppression of the HPA axis by dexamethasone in depressed patients suggests that this increased CRF secretion may be due, at least in part, to altered feedback inhibition by glucocorticoids. Because glucocorticoid-induced feedback inhibition of the HPA axis is mediated by glucocorticoid receptors (GRs) in the brain and pituitary, the possibility that depression is associated with a primary alteration in GRs number and/or function has been an important consideration regarding the pathophysiology of the depressive disorders. Nevertheless, studies investigating GRs kinetics in depressed patients have been inconsistent. In some studies, decreased GRs number in depressed patients has been observed; others have obtained discordant results. The inconsistency of results may be due to a number of factors, including patient heterogeneity, the cell populations sampled, and the methods used to determine receptors number. Fewer studies have investigated the functional sensitivity of cells to the inhibitory effects of glucocorticoids, but they have been more consistent, showing increased resistance of cells from depressed patients to the inhibitory effects of glucocorticoids on immune function. In view of intriguing data indicating monoamine regulation of GR number and function in a hormone independent fashion along with the well-known effects of glucocorticoids on behavior, further scrutiny of the role of GR in depression and its treatment is warranted.

Original languageEnglish (US)
Pages (from-to)705-712
Number of pages8
JournalIsrael journal of medical sciences
Volume31
Issue number12
StatePublished - Dec 1 1995
Externally publishedYes

Keywords

  • Adrenal hormones
  • Glucocorticoid receptor
  • Hypothalamic-pituitary-adrenal axis
  • Major depressive disorder

ASJC Scopus subject areas

  • Bioengineering
  • Medicine(all)

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    Pariante, C. M., Nemeroff, C. B., & Miller, A. H. (1995). Glucocorticoid receptors in depression. Israel journal of medical sciences, 31(12), 705-712.