Glucocorticoid hormones play a pivotal role in countless processes in the brain at the molecular, cellular, physiological, and behavioral level. In view of their widespread influence, a tight control of glucocorticoid action is of great importance. Evidence has been accumulating that the action of glucocorticoid hormones is controlled in multiple ways. Overall, it seems that glucocorticoid action is checked at roughly three levels: (1) system physiological control of the concentration of circulating, biologically available glucocorticoid hormone and its access to the brain; (2) regulation of the expression of the main mediators of glucocorticoids, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR); (3) control of MR and GR action at the effector level in terms of signaling, epigenetics, and genomics. This chapter reviews recent evidence that, at all three levels, regulatory control involves distinct epigenetic mechanisms including histone modifications, DNA methylation changes, and microRNAs, which are tissue-specific, context-dependent, and often redundant. It is clear from this assessment that, although there is still a long way to go, the elucidation of these epigenetic mechanisms in conjunction with the rapid developments in high-throughput technologies and bioinformatics will evolutionize the concepts on glucocorticoid action in the brain.
|Title of host publication||Hormones, Brain, and Behavior, Third Edition|
|Editors||Donald Pfaff, Marian Joëls|
|Publication status||Accepted/In press - 10 Jun 2016|