Glucocorticoids play an important role in the function and homeostasis of the central nervous system. Chronic exposure to supraphysiological levels of glucocorticoids in Cushing's syndrome is associated with anatomical brain changes and an increased prevalence of psychiatric diseases, cognitive impairment, mood alterations, and sleep disturbances . The effects of glucocorticoids on the nervous system and behavior will be discussed here; effects on other systems are reviewed separately. (See "Pathogenesis, clinical features, and evaluation of glucocorticoid-induced osteoporosis".)
EFFECTS ON CENTRAL NERVOUS SYSTEM
At the cellular level, glucocorticoids exert several actions on the central nervous system.
Intracellular receptors — Glucocorticoids penetrate the brain and bind to two types of intracellular receptors: glucocorticoid receptors, which are expressed in cerebral neurons and glial cells, and mineralocorticoid receptors, which are mainly expressed in limbic brain areas such as the hippocampus. Mineralocorticoid receptors bind cortisol with an affinity 10-fold higher than glucocorticoid receptors.
Low basal cortisol levels predominantly occupy high affinity mineralocorticoid receptors, whereas glucocorticoid receptors can also be activated when glucocorticoid concentrations are elevated, such as during the active period of the circadian cycle or stress, and in Cushing's syndrome [2,3].
Metabolism of glucocorticoids — Metabolism of glucocorticoids occurs intracellularly and is mediated by 11-beta-hydroxysteroid dehydrogenases (11b-HSDs) . There are two isoforms of 11b-HSDs: type 1, which elevates intracellular cortisol levels, and type 2, which inactivates glucocorticoids by converting cortisol into the inactive cortisone molecule.