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Titolo:
The brain mineralocorticoid receptor: greedy for ligand, mysterious in function
Autore:
Reul, JMHM; Gesing, A; Droste, S; Stec, ISM; Weber, A; Bachmann, C; Bilang-Bleuel, A; Holsboer, F; Linthorst, ACE;
Indirizzi:
Max Planck Inst Psychiat, Sect Neuropsychopharmacol, D-80804 Munich, Germany Max Planck Inst Psychiat Munich Germany D-80804 D-80804 Munich, Germany
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 1-3, volume: 405, anno: 2000,
pagine: 235 - 249
SICI:
0014-2999(20000929)405:1-3<235:TBMRGF>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
CORTICOTROPIN-RELEASING-HORMONE; PITUITARY-ADRENOCORTICAL AXIS; HIPPOCAMPAL SEROTONERGIC NEUROTRANSMISSION; CORTICOSTEROID-BINDING GLOBULIN; ADRENAL-STEROID RECEPTORS; MESSENGER-RNA EXPRESSION; MDR1A P-GLYCOPROTEIN; HIGH FAMILIAL RISK; RAT-BRAIN; GLUCOCORTICOID RECEPTOR;
Keywords:
mineralocorticoid receptor; glucocorticoid receptor; hypothalamic-pituitary-adrenocortical axis; stress; antidepressants; major depression;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
115
Recensione:
Indirizzi per estratti:
Indirizzo: Reul, JMHM Max Planck Inst Psychiat, Sect Neuropsychopharmacol, Kraepelinstr 2, D-80804 Munich, Germany Max Planck Inst Psychiat Kraepelinstr 2 Munich Germany D-80804
Citazione:
J.M.H.M. Reul et al., "The brain mineralocorticoid receptor: greedy for ligand, mysterious in function", EUR J PHARM, 405(1-3), 2000, pp. 235-249

Abstract

Glucocorticoids exert their regulatory effects on the hypothalamic-pituitary-adrenocortical axis via two types of corticosteroid receptors: the glucocorticoid receptor and the mineralocorticoid receptor. Whereas the glucocorticoid receptor has a broad distribution in the brain, highest levels of mineralocorticoid receptor are found in the hippocampus. Based on the differential occupancy profile by endogenous glucocorticoids, glucocorticoid receptors are thought to mediate negative feedback signals of elevated glucocorticoid levels, whereas mineralocorticoid receptors control the inhibitory tone of the hippocampus on hypothalamic-pituitary-adrenocortical axis activity. Dysfunction of mineralocorticoid receptors and glucocorticoid receptors are thought to be implicated in stress-related psychiatric diseases such asmajor depression. Because of its intriguing features, we focus in this review on the mineralocorticoid receptor and provide data which reveal novel aspects of the pharmacology and physiology of mineralocorticoid receptors. Newly obtained results are presented, which help to solve the paradox of whydexamethasone binds with high affinity to mineralocorticoid receptors in vitro, yet binds poorly in vivo. Until recently, mineralocorticoid receptor protein and mRNA levels could only be routinely studied with in vitro cytosol binding assays, in vitro and in vivo receptor autoradiography, Northern blot analysis, and in situ hybridization. These methods are unfortunately hampered by several flaws, such as the necessity of adrenalectomy, no or poor neuroanatomical resolution, the fact that mRNA does not provide the same information as protein, or combinations of these factors. We present immunohistochemical data on mineralocorticoid receptors in the brain obtained by using commercially available antibodies, which alleviate many of these shortcomings. Furthermore, an in vivo microdialysis method is presented which allows the assessment of free corticosterone levels in the brain, which is critical for the study of the pharmacological basis of mineralocorticoid receptor (and glucocorticoid receptor) function. Finally, a novel aspect of the regulation of mineralocorticoid receptors is described which provides evidence that this receptor system is dynamically regulated. In conjunction with previously reported effects of antidepressants, these results have initiated a new concept on the cause of the hypothalamic-pituitary-adrenocortical axis disturbances often seen in stress-related psychiatric disorders suchas major depression. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 16:01:09