Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress
Section snippets
Physiology of the stress response
Life exists by maintaining a complex dynamic equilibrium or homeostasis that is constantly challenged by intrinsic or extrinsic adverse forces, the stressors [1]. Under favorable conditions, individuals can be invested in vegetative and pleasurable functions that enhance their emotional and intellectual growth and development and the survival of their species, such as food intake and sex. In contrast, activation of the stress response during threatening situations that are beyond the control of
Regulation of the stress response
The orchestrated interplay of several neurotransmitter systems in the brain underlies the characteristic phenomenology of behavioral, endocrine, autonomic and immune responses to stress [28]. These transmitters include CRH, AVP, opioid peptides, dopamine and norepinephrine.
HPA axis–immune system interactions
It has been known for several decades that stress, whether inflammatory, traumatic or psychological, is associated with concurrent activation of the HPA axis. In the early 1990s, it also became apparent that cytokines and other humoral mediators of inflammation are potent activators of the central stress response, constituting the afferent limb of a feedback loop through which the immune/inflammatory system and the CNS communicate [34].
All three inflammatory cytokines, tumor necrosis factor-α
HPA axis: pathophysiology
Generally, the stress response with the resultant activation of the HPA axis is meant to be acute or at least of a limited duration. The time-limited nature of this process renders its accompanying antireproductive, antigrowth, catabolic and immunosuppressive effects temporarily beneficial rather than damaging. In contrast, chronicity of stress system activation would lead to the syndromal state that Selye described in 1936 [4]. Because CRH coordinates behavioral, neuroendocrine and autonomic
Future directions
There has been a long search for small molecular weight CRH antagonists that could be absorbed orally and cross the blood brain barrier to treat disorders characterized by a hyperactive CRH neuron as in melancholic depression. Antalarmin, a prototype CRH receptor type 1 antagonist, shows that this concept bears merit [5], [28]. This small pyrrolopyrimidine compound, binds with high affinity to the CRH receptor type 1, decreases the activity of the HPA axis and LC/NE, blocks the development and
References (47)
Regulation and dysregulation of the hypothalamic–pituitary–adrenal axis: the corticotropin releasing hormone perspective
Endocrinol Metab Clinics NA
(1992)- et al.
Physiology of the hypothalamic–pituitary–adrenal axis in health and dysregulation in psychiatric and autoimmune disorders
Endocrinol Metab Clin North Am
(1994) - et al.
Neuroendocrinology of stress
Endocrinol Metab Clin North Am
(2001) - et al.
Stimulation of hypothaIamic β-endorphin and dynorphin release by corticotropin-releasing factor
Brain Res
(1986) - et al.
Psychological stress increases arousal through brain corticotropin-releasing hormone without significant increase in adrenocorticotropin and catecholamine secretion
Brain Res
(1993) - et al.
Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development
Neuron
(1998) - et al.
The concepts of stress system disorders: overview of behavioral and physical homeostasis
JAMA, J Am Med Assoc
(1992) A syndrome produced by diverse nocuous agents
Nature
(1936)- et al.
Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates
Proc Natl Acad Sci USA
(2000) - et al.
Clinical and biochemical manifestations of depression: relationship to the neurobiology of stress. Part 1
N Engl J Med
(1988)
Clinical and biochemical manifestations of depression: relationship to the neurobiology of stress. Part 2
N Engl J Med
Amygdala: role in autonomic and neuroendorine responses to stress
Stress and the mesocorticolimbic dopamine systems
Ann NY Acad Sci
Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin
Science
Corticotropin releasing factor and vasopressin exert a synergistic effect on adrenocorticotropin release in man
J Clin Endocrinol Metab
Studies of the secretion of corticotropin releasing factor and arginine vasopressin into hypophyseal portal circulation of the conscious sheep
Neuroendocrinology
Patterns of ACTH and cortisol pulsatility over twenty-four hours in normal males and females
Clin Endocrinol
A healthy body in a healthy mind—and vice versa—the damaging power of “uncontrollable” stress
J Clin Endocrinol Metab
Magnocellular axons in passage through the median eminence release vasopressin
Nature
Functions of angiotensin II the central nervous system
Ann Rev Physiol
Paracrine control of adrenocortical function: a new role for the medulla?
J Endocrinol
Adrenal innervation may be an extrapituitary mechanism able to regulate adrenocortical rhythmicity in rats
Endocrinology
Brain corticosteroid receptor balance and homeostatic control
Front Neuroendocrinol
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“Stress” is defined as a state of disharmony or threatened homeostasis. The concepts of stress and homeostasis can be traced back to ancient Greek history, however, the integration of these notions with related physiologic and pathophysiologic mechanisms and their association with specific illnesses are much more recent.
In the present overview, we focus on the cellular and molecular infrastructure of the physiologic and behavioral adaptive responses to stress and we define the pathophysiologic effects of the dysregulation of the stress response, which may result in vulnerability to several disease entities, such as anxiety or depression and chronic inflammatory processes.