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Functional profile of the binary brain corticosteroid receptor system: Mediating, multitasking, coordinating, integrating
- Source :
- European Journal of Pharmacology, 719(1-3), 53-62
- Publication Year :
- 2013
-
Abstract
- This contribution is focused on the action of the naturally occurring corticosteroids, cortisol and corticosterone, which are secreted from the adrenals in hourly pulses and after stress with the goal to maintain resilience and health. To achieve this goal the action of the corticosteroids displays an impressive diversity, because it is cell-specific and context-dependent in coordinating the individual's response to changing environments. These diverse actions of corticosterone are mediated by mineralocorticoid- and glucocorticoid-receptors that operate as a binary system in concert with neurotransmitter and neuropeptide signals to activate and inhibit stress reactions, respectively. Classically MR and GR are gene transcription factors, but recently these receptors appear to mediate also rapid non-genomic actions on excitatory neurotransmission suggesting that they integrate functions over time. Hence the balance of receptor-mediated actions is crucial for homeostasis. This balanced function of mineralo- and glucocorticoid-receptors can be altered epigenetically by a history of traumatic (early) life events and the experience of repeated stressors as well as by predisposing genetic variants in signaling pathways of these receptors. One of these variants, mineralocorticoid receptor haplotype 2, is associated with dispositional optimism in appraisal of environmental challenges. Imbalance in receptor-mediated corticosterone actions was found to leave a genomic signature highlighting the role of master switches such as cAMP response element-binding protein and mammalian target of rapamycin to compromise health, and to promote vulnerability to disease. Diabetic encephalopathy is a pathology of imbalanced corticosterone action, which can be corrected in its pre-stage by a brief treatment with the antiglucocorticoid mifepristone.
- Subjects :
- Receptors, Steroid
medicine.medical_specialty
medicine.drug_class
Neurotransmission
Stress
chemistry.chemical_compound
Cognition
Mineralocorticoid receptor
Glucocorticoid receptor
Corticosterone
Internal medicine
Diabetes Mellitus
medicine
Animals
Humans
Neurotransmitter
Receptor
Glucocorticoids
Pharmacology
Behavior
Genome
Depression
Diabetes
Brain
Endocrinology
chemistry
Mineralocorticoid
Signal transduction
Psychology
Neuroscience
Stress, Psychological
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology, 719(1-3), 53-62
- Accession number :
- edsair.doi.dedup.....bf53065cf1827939c726fb52f5f2254b