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Novel Aspects of Glucocorticoid Actions
Author(s) -
Uchoa E. T.,
Aguilera G.,
Herman J. P.,
Fiedler J. L.,
Deak T.,
Sousa M. B. C.
Publication year - 2014
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12157
Subject(s) - medicine , endocrinology , vasopressin , orexigenic , glucocorticoid , biology , hypothalamus , glucocorticoid receptor , neuroscience , hippocampal formation , neuropeptide , receptor , neuropeptide y receptor
Normal hypothalamic‐pituitary‐adrenal ( HPA ) axis activity leading to the rhythmic and episodic release of adrenal glucocorticoids ( GC s) is essential for body homeostasis and survival during stress. Acting through specific intracellular receptors in the brain and periphery, GC s regulate behaviour, as well as metabolic, cardiovascular, immune and neuroendocrine activities. By contrast to chronic elevated levels, circadian and acute stress‐induced increases in GC s are necessary for hippocampal neuronal survival and memory acquisition and consolidation, as a result of the inhibition of apoptosis, the facilitation of glutamatergic neurotransmission and the formation of excitatory synapses, and the induction of immediate early genes and dendritic spine formation. In addition to metabolic actions leading to increased energy availability, GC s have profound effects on feeding behaviour, mainly via the modulation of orexigenic and anorixegenic neuropeptides. Evidence is also emerging that, in addition to the recognised immune suppressive actions of GC s by counteracting adrenergic pro‐inflammatory actions, circadian elevations have priming effects in the immune system, potentiating acute defensive responses. In addition, negative‐feedback by GC s involves multiple mechanisms leading to limited HPA axis activation and prevention of the deleterious effects of excessive GC production. Adequate GC secretion to meet body demands is tightly regulated by a complex neural circuitry controlling hypothalamic corticotrophin‐releasing hormone ( CRH ) and vasopressin secretion, which are the main regulators of pituitary adrenocorticotrophic hormone ( ACTH ). Rapid feedback mechanisms, likely involving nongenomic actions of GC s, mediate the immediate inhibition of hypothalamic CRH and ACTH secretion, whereas intermediate and delayed mechanisms mediated by genomic actions involve the modulation of limbic circuitry and peripheral metabolic messengers. Consistent with their key adaptive roles, HPA axis components are evolutionarily conserved, being present in the earliest vertebrates. An understanding of these basic mechanisms may lead to novel approaches for the development of diagnostic and therapeutic tools for disorders related to stress and alterations of GC secretion.