Function and plasticity of brain corticosteroid receptor systems: action of neuropeptides

Two types of corticosteroid receptors may be distinguished in rat brain. Type 1 resembles the kidney mineralocorticoid receptor and Type 2 is similar to the liver glucocorticoid receptor (GR). Type 1 receptor system displays two functional expressions, i.e. Type 1 corticosterone (CORT)-preferring sites (CR) and Type 1 mineralocorticoid receptors (MR). MR occurs in circumventricular organs and mediates behaviors such as salt appetite. CR has its principal localization in neurons of the hippocampus, and mediates tonic influences of CORT on hippocampus-associated functions. CR responds with stringent specificity to CORT. Differentiation between CR and MR is due to a different accessibility of the receptor by CORT and ALDO, which seems dependent on the presence of extravascular corticosteroid binding globulin (CBG). GR has a wide distribution in brain, occurs in neurons and glial cells and has its principal localization in such regions as the paraventricular nucleus and the n. tractus solitarii (site of CRF synthesis and of blood pressure regulation, respectively). GR mediates the feedback action of CORT on stress-activated brain processes. GR is subject to autoregulation by CORT. Chronic stress, senescence, and chronic CORT administration reduce receptor number, while GR capacity is increased after adrenalectomy. Reduced GR receptor number results in a less-efficient feedback action. The CORT signal via CR probably can only be altered via changes in CR density evoked rather by neural factors than by autoregulation. CR density is reduced at senescence, but is increased to receptor number of young control animals after chronic treatment with a behaviorally potent ACTH-(4-9) analogue, Org 2766. CR plasticity is prominent for the hippocampus, which is a structure involved in cognition, emotional state and subtle regulation of pituitary-adrenal function.