Central corticosteroid actions: Search for gene targets

Although many of the physiological effects of corticosteroid stress hormones on neuronal function are well recognised, the underlying genomic mechanisms are only starting to be elucidated. Linking physiology and genomics has proven to be a complicated task, despite the emergence of large-scale gene expression profiling technology in the last decade. This is in part due to the complexity of glucocorticoid-signaling, in part due to the complexity of the brain itself. The presence of a binary receptor system for glucocorticoid hormones in limbic brain structures, the coexistence of membrane and intracellular receptors and the highly contextual action of glucocorticoids contribute to this complexity. In addition, the anatomical complexity, extensive cellular heterogeneity of brain and the modest changes in gene expression (mostly in the range of 10–30%) hamper detection of responsive genes, in particular of low abundant transcripts, such as many neurotransmitter receptors and growth factors. Nonetheless, ongoing research into central targets of glucocorticoids has identified many different functional gene classes that underlie the diverse effects of glucocorticoids on brain function. These functional classes include genes involved in energy metabolism, signal transduction, neuronal structure, vesicle dynamics, neurotransmitter catabolism, cell adhesion, genes encoding neurotrophic factors and their receptors and genes involved in regulating glucocorticoid-signalling. The aim of this review is to give an overview of the current status of the field on identification of central corticosteroid targets, discuss the opportunities and pitfalls and highlight new developments in understanding central corticosteroid action.