The central CLOCK system and the stress axis in health and disease

Abstract

are secreted in the portal system in a circadian and highly concordant pulsatile fashion. The activity of the HPA axis is in fact characterized not only by a classic circadian rhythm, but also by an ultradian pattern of discrete pulsatile release of glucocorticoids. Glucocorticoids are the final effectors of the HPA axis. These hormones are pleiotropic and exert their effects through their ubiquitously distributed intracellular glucocorticoid receptors alpha and beta (GRα and GRβ, respectively), both members of the nuclear receptor superfamily.2 The circadian release of ACTH/cortisol in their characteristic pulsatile manner appears to be controlled by one or more pace makers, whose exact location in the brain has not as yet been fully explored in humans. These diurnal variations are perturbed during daily activities like eating, sleeping, etc., while they are more greatly disrupted under stress conditions. Dysregulation of the HPA axis in basal conditions or in response to acute or chronic (including psychosocial) stress appear to be closely related to the onset and/or the progression of several diseases, such as metabolic syndrome, depression, and autoimmune diseases.Herein, we aim to review the current knowledge of the mechanisms that regulate ACTH and cortisol secretion under nonstressful conditions maintaining homeostasis as well as in stressful circumstances in an attempt to delineate the involvement of the 'stressresponse' component in disorders afflicting a large number of people.

Individual Differences in Stress Responsiveness of the Hypothalamic-Pituitary-Adrenal Axis and Its Vasopressinergic Regulation in Old Monkeys

“…Hypercortisolemia plays a pathophysiological role in the development of a variety of stress-related diseases: psychiatric, reproductive, immune, metabolic, and others. It is a major factor in aging and age-related pathology [4] [40] [41]. For example, we have previously identified more severe disturbances of antioxidant enzyme defense of erythrocytes and higher values of the molar ratio F/DHEAS in old animals with depression-like adaptive behavior as compared with animals of the same age but with SB [33].…”

Clock genes and cancer development in particular in endocrine tissues

“…Circadian rhythms are biological rhythms that exhibit a periodicity close to 24 h. In mammals, these rhythms are generated by a master biological clock, located centrally in the suprachiasmatic nucleus (SCN) of the hypothalamus and by clocks localized in peripheral tissues (Lowrey & Takahashi 2011, Kassi et al 2013. Both clocks communicate with each other and generate circadian rhythmicity by the coordinated activation/inactivation of self-oscillating transcription factors (Charmandari et al 2011).…”

Effects of acute stress on aggression and the cortisol response in the African sharptooth catfish Clarias gariepinus: differences between day and night

“…The onset of light initiates the synchronization of many biological processes that follow a circadian rhythm (Roenneberg & Merrow, 2005), among them the stress-axis, also known as the hypothalamus-pituitary-interrenal (HPI) axis (Nader et al, 2010). Changes in the circadian rhythm of cortisol, the corticosteroid produced by the HPI-axis, due to changing the day-night cycle, can result in inadequate responses to challenges (Weibel et al, 2002;Kassi & Chrousos, 2013), and may lead to compensatory hyperactivity of other mediators (McEwen, 2000). Farmed fishes are potentially exposed to a multitude of challenges, such as handling (Manuel et al, 2014), poor water quality (Roques, 2013), inappropriate stocking densities (Kaiser et al, 1995;van de Nieuwegiessen et al, 2008) and live transport (Iversen et al, 2005;Nomura et al, 2009;Brinn et al, 2012;Nikoo & Falahatkar, 2012;Manuel et al, 2014;Boerrigter et al, 2015a).…”