What we collectively call “stress” is how we experience our body’s reaction to a stressor. This response is aimed to deal with the current stressor and to prepare for recurrences in the future. The... Show moreWhat we collectively call “stress” is how we experience our body’s reaction to a stressor. This response is aimed to deal with the current stressor and to prepare for recurrences in the future. The stress response is for an important part dependent on glucocorticoid hormones. By and large, the acute response to glucocorticoids is beneficial, but chronic exposure often becomes maladaptive. To improve prevention and treatment of disorders we can develop due to stress, it is important to better understand the effects and working mechanisms of glucocorticoids. While we already possess extensive knowledge regarding glucocorticoids and glucocorticoid receptor signaling, we introduced and studied five “aspects of context”, which we felt address important current misconceptions or gaps of knowledge. Corticosterone was at the center of all the studies we performed, yet the eventual outcome of glucocorticoid receptor activation differed extensively in all experiments. Thus, the context in which corticosterone exerts its effects matters, and it is to researcher to be aware of this when designing new studies and interpreting available data. Whilst our research merely addressed some specific processes, the lessons learned from these experiments can be applied much broader to the biology of glucocorticoid signaling and other nuclear family members. Show less
Corticosteroid hormones act in the brain to support adaptation to stress via binding to mineralocorticoid and glucocorticoid receptors (MR and GR). These receptors act in large measure as... Show moreCorticosteroid hormones act in the brain to support adaptation to stress via binding to mineralocorticoid and glucocorticoid receptors (MR and GR). These receptors act in large measure as transcription factors. Corticosteroid effects can be highly divergent, depending on the receptor type, but also on brain region, cell type, and physiological context. These differences ultimately depend on differential interactions of MR and GR with other proteins, which determine ligand binding, nuclear translocation, and transcriptional activities. In this review, we discuss established and potential mechanisms that confer receptor and cell type-specific effects of the MR and GR-mediated transcriptional effects in the brain. Show less
