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Hormones as Immune Modulating Agents
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Corticotropin releasing factor stimulates the release of ACTH from the pituitary gland and mediates, in part, cytokine-induced ACTH release from the pituitary gland. It is a major stress response that integrates peptide of the central nervous system and acts centrally as an immunosuppressive agent, which is not mediated by glucocorticoids but rather by the stimulation of sympathetic outflow. Receptors for CRF are present in the immune system and immunocytes produce CRF [140,141].
Global prevalence and international perspective of paediatric gastrointestinal disorders
Published in Clarissa Martin, Terence Dovey, Angela Southall, Clarissa Martin, Paediatric Gastrointestinal Disorders, 2019
Shaman Rajindrajith, Niranga Devanarayana, Marc Benninga
Psychological factors are well recognised as principal contributory factors to the development of FGIDs in children. Psychological stress is known to alter receptor functions of the central corticotropin-releasing factor signalling system, inducing acute and chronic stress-induced visceral hyperalgesia. This is thought to be a major pathophysiological mechanism for the development of functional gastrointestinal diseases (Mayer and Tillisch, 2011). Stressful life events have become a common problem in the day-to-day lives of children. A series of epidemiological investigations from Sri Lanka has shown that several FGIDs are associated with school- and home-related stress (Devanarayana et al., 2011b; Rajindrajith and Devanarayana, 2012; Devanarayana and Rajindrajith, 2010). In addition, other studies on Asiatic populations have shown that frequency of IBS is increased in children exposed to stress (Endo et al., 2011; Son et al., 2009).
Pathophysiological Mechanisms of Chronic Pelvic Pain
Published in Linda Cardozo, Staskin David, Textbook of Female Urology and Urogynecology - Two-Volume Set, 2017
in pAin. P2X3 knockout mice hAve Urinary blAdder hyporeflexiA with increAsed voiding volume And decreAsed voiding frequency And decreAsed inflAmmAtory pAin [70,71]. The corticotropin-releAsing fActor (CrF) receptor is involved in the stress response, ActivAting the hypothAlAmic–pituitAry– AdrenAl (HPA) And sympAthoAdrenAl Axes. Women with chronic pelvic pAin demonstrAte HPA Axis AlterAtions similAr to pAtients with other stress-relAted bodily disorders [72]. enhAnced pelvic responses to stressors hAve been demonstrAted in CrF-overexpressing mice [73]. opioids constitute A mAjor clAss of AnAlgesics to treAt viscerAl pAin. nociceptin– orphAnin receptor Agonists hAve been used in preclinicAl models of pelvic pAin with promising potentiAl for therApeutic effects. This AntihyperAlgesic effect does not involve A Cns site of Action [74]. In summAry, modulAtion of viscerAl nociceptive pAthwAys cAn occur At peripherAl, spinAl, And suprAspinAl sites. There is A concerted effort underwAy to develop tArget-specific viscerAl AnAlgesics for the treAtment of chronic pelvic pAin [75]. However, bAsed on the recognition thAt chronic pelvic is A heterogeneous group of conditions And leArning from previously fAiled clinicAl triAls, the discovery of A single tArget for the treAtment of chronic pelvic pAin is unlikely. A key issue for the success of future clinicAl triAls will be improved pAtient phenotyping to identify subgroups of pAtients with chronic pelvic pAin, bAsed on Aspects such As clinicAl symptoms, quAntitAtive sensory testing pArAmeters, biomArkers, And comorbid conditions.
Pharmacological Treatment of Generalised Anxiety Disorder: Current Practice and Future Directions
Published in Expert Review of Neurotherapeutics, 2023
Harry A. Fagan, David S. Baldwin
Corticotropin-releasing factor/hormone (CRF/CRH) is a peptide hormone secreted by the hypothalamus in response to stress. It stimulates secretion of adrenocorticotropic hormone (ACTH) by the anterior pituitary and is a component of the hypothalamic-pituitary-adrenal (HPA) axis. CRF binds two different GPCR (CRF1 and CRF2 receptors) which are expressed in the hypothalamus and other brain regions [117]. An anxiogenic (and pro-depressive) role of CRF1 receptors was identified in animal studies, leading to the development of several CRF1 receptor antagonists [117,118]. However, clinical studies of CRF1 receptor antagonists have not shown promise in anxiety disorders [118]. To date, only one RCT has been published in GAD, which showed that the CRF1 receptor antagonist pexacerfont did not differentiate from placebo treatment after 8 weeks of treatment [119].
Restraint stress induces uterine microenvironment disorder in mice during early pregnancy through the β2-AR/cAMP/PKA pathway
Published in Stress, 2021
Jiayin Lu, Guanhui Liu, Zixu Wang, Jing Cao, Yaoxing Chen, Yulan Dong
A study of schizophrenia and PTSD demonstrated that the corticotropin-releasing factor (CRF) and NE systems, both of which are activated by stress, are the most widely implicated systems in stress-induced psychopathology (Rajbhandari et al., 2015). In our work, we found that NE levels decreased as the gestational age increased (Figure 2(C)). After restraint stress, NE concentrations at E3, E5 and E7 were significantly increased. The activation of noradrenergic (NE) receptors increases the risk of pregnancy-induced hypertension (Newport et al., 2016). Additionally, gluconeogenesis is usually enhanced by glucocorticoids and then increases blood glucose levels (Fagerholm et al., 2008). In our previous study, CORT was increased in early pregnancy under restraint stress (Liu et al., 2014). In this work, blood glucose levels were increased under the restraint stress at three gestational ages (Figure 2(B)), suggesting a high risk for gestational diabetes. Restraint stress results in a decrease in body weight due to a massive consumption of energy and a continuous reduction in body temperature (Jeong et al., 2013). Therefore, diabetes may gradually reduce body weight and maintain normal functions of the body (Komorita et al., 2018). In our study, the reduction in body weight was increased early after restraint stress (Figure 2(A)). Furthermore, body weight decreases, possibly causing embryonic growth retardation (Liu et al., 2014).
Stress and Western diets increase vulnerability to neuropsychiatric disorders: A common mechanism
Published in Nutritional Neuroscience, 2021
The organization of stress responses is mainly regulated by two primary systems: the autonomic nervous system and the hypothalamus–pituitary–adrenal (HPA) axis [10]. The activity of the sympathetic nervous system increases during eustress, allowing catecholamines to be released from the adrenal medulla into the bloodstream (Scheme 1). This triggers autonomic responses that allow an increase of heart rate, blood pressure, and glucose availability, which in turn deliver energetic substrates to face the threat, inducing the fight or flight stress responses for adaptation [10]. At the same time, the HPA axis is activated, redirecting the metabolism to supply the energy requirements demanded by stress responses [11]. Stressors increase the release of corticotropin-releasing factor (CRF) from the hypothalamus to the anterior pituitary, inducing the release of the adrenocorticotropic hormone (ACTH) to the bloodstream. This hormone stimulates the secretion of glucocorticoids (GC) from the adrenal cortex, which are bound to glucocorticoid receptors (GR) in peripheral tissues and brain (Scheme 1). The main GC of stress responses are cortisol in humans and corticosterone in rodents [10]. GC act on the brain as part of the negative feedback mechanism that inhibits the activity of the HPA axis when animals adapt to the stressors (Scheme 1). On the other hand, CRF also acts in different extra-hypothalamic areas modulating stress responses [12–14].