Corticosteroid Action in the Brain: The Potential of Selective Receptor Modulation.

Abstract:

:Glucocorticoid hormones have important effects on brain function in the context of acute and chronic stress. Many of these are mediated by the glucocorticoid receptor (GR). GR has transcriptional activity which is highly context-specific and differs between tissues and even between cell types. The outcome of GR-mediated transcription depends on the interactome of associated coregulators. Selective GR modulators (SGRMs) are a class of GR ligands that can be used to activate only a subset of GR-coregulator interactions, thereby giving the possibility to induce a unique combination of agonistic and antagonistic GR properties. We describe SGRM action in animal models of brain function and pathology, and argue for their utility as molecular filters, to characterize context-specific GR interactome and transcriptional activity that are responsible for particular glucocorticoid-driven effects in cognitive processes such as memory consolidation. The ultimate objective of this approach is to identify molecular processes that are responsible for adaptive and maladaptive effects of glucocorticoids in the brain.

journal_name

Neuroendocrinology

journal_title

Neuroendocrinology

authors

Viho EMG,Buurstede JC,Mahfouz A,Koorneef LL,van Weert LTCM,Houtman R,Hunt HJ,Kroon J,Meijer OC

doi

10.1159/000499659

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

266-276

issue

3

eissn

0028-3835

issn

1423-0194

pii

000499659

journal_volume

109

pub_type

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