The stress response and the hypothalamic-pituitary-adrenal axis:
from molecule to melancholia

O'Connor TM, O'Halloran DJ, Shanahan F
Departments of Endocrinology and Medicine,
Cork University Hospital and University College Cork,
Cork, Ireland.
QJM 2000 Jun; 93(6):323-333


Organisms survive by maintaining equilibrium with their environment. The stress system is critical to this homeostasis. Glucocorticoids modulate the stress response at a molecular level by altering gene expression, transcription, and translation, among other pathways. The effect is the inhibition of the functions of inflammatory cells, predominantly mediated through inhibition of cytokines, such as IL-1, IL-6, and TNF-alpha. The central effectors of the stress response are the corticotrophin-releasing hormone (CRH) and locus coeruleus-norepinephrine (LC-NE)/sympathetic systems. The CRH system activates the stress response and is subject to modulation by cytokines, hormones, and neurotransmitters. Glucocorticoids also modulate the growth, reproductive and thyroid axes. Abnormalities of stress system activation have been shown in inflammatory diseases such as rheumatoid arthritis, as well as behavioural syndromes such as melancholic depression. These disorders are comparable to those seen in rats whose CRH system is genetically abnormal. Thus, the stress response is central to resistance to inflammatory and behavioural syndromes. In this review, we describe the response to stress at molecular, cellular, neuroendocrine and behavioural levels, and discuss the disease processes that result from a dysregulation of this response, as well as recent developments in their treatment.
Cushing's syndrome
Stress and aggression
Glucocorticoids and mood
Hippocampal remodelling
Stress, BDNF and the brain
Neuroendocrinology of stress
Stress, depression and anxiety
HPA axis, serotonin and suicide
Depression, opioids and the HPA
Antidepressants and new brain cells
The corticosteroid hypothesis of depression
An overactive immune system and depression
Stress and CRH, corticosteroids and monoamines
Stress, glucocorticoid receptor loss and depression
Stress, dynorphin, dysphoria and the kappa opioid system

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