Steroid effects on central neurons and implications for psychiatric and neurological disorders.
Acute and chronic stress as well as a number of psychiatric and neurological disorders are accompanied by profound disturbances of the HPA system. These neuroendocrine alterations act back on the central nervous tissue mainly via corticosteroids-affecting glucocorticoid and mineralocorticoid receptors. The major conclusions drawn from studies probing these receptors in clinical investigations are: (1) In many such conditions central corticosteroid receptors are weakened in their capacity to curtail spontaneous and stress-elevated corticosteroid levels; (2) the combined DEX-CRH test is the best neuroendocrine tool currently available for identifying HPA abnormalities in psychiatric patients; (3) in depression the decreased corticosteroid receptor capacity in transient, and antidepressants act through reinstatement of GR and MR function probably resulting in reduced hypothalamic CRH and AVP production; (4) several neurological disorders such as MS and HIV infection are often accompanied by altered HPA function, which has therapeutic implications; and (5) various corticosteroids, their biosynthetic precursors and their metabolites have differentiable effects on the sleep EEG, which can be attributed to their mode of action; specifically, steroids such as pregnenolone and DHEA most likely are produced in glia cells and act in a paracrine fashion at neurons, thus modifying the sleep EEG in humans in a manner that suggests their potential as memory enhancers.
Holsboer
F
F
Max Planck Institute of Psychiatry Clinical Institute, Munich, Germany.
Grasser
A
A
Friess
E
E
Wiedemann
K
K
D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000639:Amitriptyline / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D001921:Brain / Q000502:physiology / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone; D003907:Dexamethasone; D004569:Electroencephalography / Q000187:drug effects; D015658:HIV Infections / Q000503:physiopathology; D006801:Humans; D006854:Hydrocortisone / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology / Q000503:physiopathology*; D020912:Moclobemide; D019964:Mood Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology / Q000503:physiopathology*; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology*; D013315:Stress, Psychological / Q000503:physiopathology; D014947:Wounds and Injuries / Q000503:physiopathology*
D001549:Benzamides; D000639:Amitriptyline; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D020912:Moclobemide; D006854:Hydrocortisone