Stress, the Stress System and the Role of Glucocorticoids

Abstract

All living organisms have developed a highly conserved and regulatory system, the stress system, to cope with a broad spectrum of stressful stimuli that threaten, or are perceived as threatening, their dynamic equilibrium or homeostasis. This neuroendocrine system consists of the hypothalamic-pituitary-adrenal (HPA) axis and the locus caeruleus/norepinephrine-autonomic nervous system. In parallel with the evolution of the homeostasis and stress concepts from ancient Greek to modern medicine, significant advances in the field of neuroendocrinology have identified the physiologic biochemical effector molecules of the stress response. Glucocorticoids, the end-products of the HPA axis, play a fundamental role in the maintenance of both resting and stress-related homeostasis and, undoubtedly, influence the physiologic adaptive reaction of the organism against stressors. If the stress response is dysregulated in terms of magnitude and/or duration, homeostasis is turned into cacostasis with adverse effects on many vital physiologic functions, such as growth, development, metabolism, circulation, reproduction, immune response, cognition and behavior. A strong and/or long-lasting stressor may precipitate and/or cause many acute and chronic diseases. Moreover, stressors during pre-natal, post-natal or pubertal life may have a critical impact on our expressed genome. This review describes the central and peripheral components of the stress system, provides a comprehensive overview of the stress response, and discusses the role of glucocorticoids in a broad spectrum of stress-related diseases.

Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)

“…Systemic inflammation-a central component of the innate immune system-is a highly organized response to infectious and non-infectious threats to homeostasis that consists of at least three major domains: (1) the stress system mediated by the HPA axis and the locus coeruleus-norepinephrine/sympathetic nervous system, (2) the acute-phase reaction, and (3) the target (vital organs) tissue defense response [2,3]. Whereas appropriately regulated inflammation-tailored to stimulus and time [4]-is beneficial, excessive or persistent systemic inflammation incites tissue destruction and disease progression [5].…”

“…The activated glucocorticoid-glucocorticoid receptor-alpha (GC-GRα) complex plays a fundamental role in the maintenance of both resting and stress-related homeostasis and influences the physiologic adaptive reaction of the organism against stressors [2]. The activated GC-GRα complex exerts its activity at the cytoplasmic level and on nuclear deoxyribonucleic acid (nDNA) and mitochondrial DNA (mtDNA) [8] affecting thousands of genes involved in response to stress and non-stress states [9].…”

Growth patterns in male rats exposed to concurrent long-term environmental challenges

“…CORT values were obtained from diethyl ether extracted plasma aliquots (15 µl) using a radioimmunoassay, following Jahn et al (1995). In addition, as the alteration of the adrenal histo-architecture is a known consequence of chronic stress (Nicolaides et al, 2015;Ulrich-Lai et al, 2006), we compared the relative masses of the zona fasciculata and zona glomerulosa from the adrenal cortex. The net and relative sizes of the zona fasciculata and zona glomerulosa were obtained by the morphometric analysis of the stained sections with hematoxylin and eosin.…”

Novel insights into the molecular mechanisms underlying generalized glucocorticoid resistance and hypersensitivity syndromes

“…[1][2][3][4] These lipophilic molecules are derived from cholesterol through serial enzymatic reactions that lead to the production of all steroid hormones. 5 For many years it was believed that glucocorticoids were exclusively synthesized in endocrine cells located in the zona fasciculata of the adrenal cortex.…”