The review article ‘Stress and disorders of the stress system’ published in Nature Reviews Endocrinology provides a brief but comprehensive overview on the conceptual evolution, and current understanding of homeostasis and the pathogenic disturbances that are associated with stress and the disorders of the stress system.
Homeostasis, a term coined by the American physiologist Walter Cannon in the beginning of the 20th century, refers to the process by which the body maintains a constant internal environment or stability of the inner world.
In the Nature Reviews Endocrinology,George Chrousos, an established expert, working in the stress research area for over 30 years, defines stressas a
state in which homeostasis is actually threatened or perceived to be so.
According to the author, “all living organisms maintain a complex dynamic equilibrium, or homeostasis”, which is constantly challenged by internal or external adverse effects, termed stressors. Stressors comprise a long list of potentially adverse forces, which can be emotional or physical. Both the magnitude and chronicity of stressors are important. When any stressor exceeds a certain severity or temporal threshold, the adaptive homeostatic systems of the organism activate compensatory responses that functionally correspond to the stressor.
Dr. Chrousos defines the central and peripheral effectors of the stress system. Thus, the principal, greatly interconnected CNS effectors of the stress system, include the hypothalamic hormones arginine vasopressin (AvP), corticotropin releasing hormone (CRH), the pro opiomelanocortin derived peptides α melanocyte stimulating hormone and β endorphin, and norepinephrine produced in the A1/A2 centers of the brainstem’s locus ceruleus and in the central, autonomic nervous system.
As per the author, the stress system interacts with, influences and is influenced by several systems in the brain that serve cognitive and/or executive, fear and anger and reward functions. These systems form a complex, integrated, positive and negative feedback system loop. Furthermore, the stress system acutely and in a temporally limited fashion activates the central nucleus of the amygdala, which has its own CRH system involved in the generation of fear and/or anger; in return, the central nucleus of the amygdala stimulates the stress system and forms a mutually reinforcing positive feedback loop.
The principal peripheral effectors are glucocorticoids, which are regulated by the hypothalamic–pituitary–adrenal axis, and the catecholamines norepinephrine and epinephrine, which are regulated by the systemic and adrenomedullary sympathetic nervous systems. Interestingly, postganglionic sympathetic nerve fibers also secrete CRH, among other substances, whereas both catecholamines stimulate interleukin-6 (IL-6) release by immune cells and other peripheral cells via β adrenergic receptors.
The author discusses the mediators and mechanisms of the stress response, and the effects of stress on arousal and sleep, metabolism, growth, reproduction, thyroid and gastrointestinal function, and the immune system.
In addition, an integrative view is given on behavioral and somatic consequences of stress, and on some mechanisms of stress-related disorders and conditions in modern societies, such as obesity, the metabolic syndrome and type 2 diabetes mellitus; hypertension; some intracellular infections, autoimmunity and allergy; anxiety, insomnia, and depression; and pain and fatigue syndromes.
Chrousos argues that in the modern societies, lifestyle has changed dramatically from that of our past, and that modern societies are plagued by “clusters of the so-called multifactorial polygenic disorders” listed above. Importantly, all these disorders appear to be associated with dysfunction of the stress system.
The malfunction of the stress system might impair growth, development, behavior and metabolism, which potentially lead to various acute and chronic disorders.
According to the author, high levels of corticotropin-releasing hormone (CRH) and/or stress system abnormalities may contribute to hypothalamic oligomenorrhea and amenorrhea, reduced fertility, anxiety, depression or posttraumatic stress disorder in children. Moreover, overproduction of CRH or disruption of the hypothalamic–pituitary–adrenal axis and the functions of the arousal and sympathetic nervous systems, are associated with obesity, metabolic syndrome and essential hypertension.
The author discusses that acute allergic attacks may be activated by immune CRH-induced degranulation of mast cells in the vulnerable organ, causing asthma or eczema, respectively. On the other hand, chronic stress may induced immune dysfunction, including a switch from T helper (Th1) to Th2 cellular responses, which may contribute to increased vulnerability of individuals to certain infections and autoimmune disorders.