Open AccessCorticosteroid Action in the Brain: The Potential of Selective Receptor Modulation
Author(s) -
Eva M. G. Viho,
Jacobus C Buurstede,
Ahmed Mahfouz,
Lisa L. Koorneef,
Lisa T. C. M. van Weert,
René Houtman,
Hazel Hunt,
Jan Kroon,
Onno Meijer
Publication year - 2019
Publication title -
neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.493
H-Index - 101
eISSN - 1423-0194
pISSN - 0028-3835
DOI - 10.1159/000499659
Subject(s) - glucocorticoid receptor , interactome , glucocorticoid , neuroscience , transcription factor , context (archaeology) , receptor , biology , endocrinology , medicine , gene , genetics , paleontology
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.