Endocrine Abstracts

Corticosteroid hormones are synthetized in the adrenal glands and reach many organs including the brain. Within the brain they exert their actions through mineralocorticoid (MR) and glucocorticoid receptors (GR). These receptors generally act as transcriptional regulators and change the function of brain cells in a slow manner, with effects appearing after approximately one hour. However, in the past decade it has become evident that corticosteroid receptors also change brain function rapidly. In an extensive series of studies we have shown that cognitive function in humans and rodents are accordingly changed in two time-domains. First, within minutes through rapid non-genomic actions (generally involving the MR), enabling organisms to quickly respond to challenging conditions by selecting a simple self-centered strategy geared to survive the situation. And secondly, with a delay of an hour, through GR-mediated gene-dependent pathways, promoting higher cognitive functions, e.g. altruistic choices which are beneficial in the future or linking stress-related information to the relevant context.

An appropriate balance between these systems is important in health and disease. For instance, down-regulation of the MR – as seen with ageing or after early life stress – is associated with higher prevalence of depression and in rodents leads to cognitive deficits. Conversely, overexpression of MR in rodents appears to protect against cognitive deficits after early life adversity. Current research is focused on effective intervention strategies around puberty, to restore the MR:GR balance and remediate effects of early life stress.