3.08 – Genomic Aspects of Corticosteroid Action in the Brain

The effects of corticosteroid hormones are mediated by two types of receptors: very high-affinity mineralocorticoid receptors (MRs) and lower affinity glucocorticoid receptors (GRs). MRs and GRs are members of the nuclear receptor family and act in large measure as transcription factors. In this chapter we describe the considerable variation in receptor expression, isoform expression, and activity status that helps fine-tuning the sensitivity of different brain circuits to corticosteroids. In addition, MR and GR effects are highly context dependent based on the variety of interacting proteins that determine the exact mode of MG/GR signaling. First, the receptors may interact with a number of other transcription factors, without binding directly to the DNA. Second, after direct binding to the DNA, MR/GR interacts with transcriptional coregulator proteins that determine the nature and magnitude of the transcriptional effects. The receptor modifications and the diversity of signaling partners form the basis of appropriate changes in gene expression that underlie the adaptive effects of corticosteroid hormones.