Stress and Disorders of the Stress System

George Chrousos

A recent article 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 stress as a “state in which homeostasis is actually threatened or perceived to be so”. He 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.

Source: Nat Rev Endocrinol 2009, 5:374
Read more: Nature Reviews Endocrinology


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