Role of glucocorticoid negative feedback in the regulation of HPA axis pulsatility

The hypothalamic-pituitary-adrenal (HPA) axis is the major neuroendocrine axis regulating homeostasis in mammals. Glucocorticoid hormones are rapidly synthesized and secreted from the adrenal gland in response to stress. In addition, under basal conditions glucocorticoids are released rhythmically w...

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Bibliographic Details
Published in:Stress (Amsterdam, Netherlands) Netherlands), 2018-09, Vol.21 (5), p.403-416
Main Authors: Gjerstad, Julia K, Lightman, Stafford L, Spiga, Francesca
Format: Article
Language:English
Subjects:
Adrenal Glands - metabolism
Animals
Circadian Rhythm - physiology
Feedback, Physiological - physiology
glucocorticoids
Glucocorticoids - metabolism
Homeostasis - physiology
Humans
Hypothalamic-pituitary-adrenal axis
Hypothalamo-Hypophyseal System - metabolism
negative feedback
Pituitary-Adrenal System - metabolism
Receptors, Glucocorticoid - metabolism
Review
Signal Transduction
ultradian rhythm
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Summary:The hypothalamic-pituitary-adrenal (HPA) axis is the major neuroendocrine axis regulating homeostasis in mammals. Glucocorticoid hormones are rapidly synthesized and secreted from the adrenal gland in response to stress. In addition, under basal conditions glucocorticoids are released rhythmically with both a circadian and an ultradian (pulsatile) pattern. These rhythms are important not only for normal function of glucocorticoid target organs, but also for the HPA axis responses to stress. Several studies have shown that disruption of glucocorticoid rhythms is associated with disease both in humans and in rodents. In this review, we will discuss our knowledge of the negative feedback mechanisms that regulate basal ultradian synthesis and secretion of glucocorticoids, including the role of glucocorticoid and mineralocorticoid receptors and their chaperone protein FKBP51. Moreover, in light of recent findings, we will also discuss the importance of intra-adrenal glucocorticoid receptor signaling in regulating glucocorticoid synthesis.
ISSN:1025-3890
1607-8888
DOI:10.1080/10253890.2018.1470238