O eixo hipotálamo-pituitária-adrenal, a função dos receptores de glicocorticóides e sua importância na depressão

Abstract

Objective: Changes in the hypothalamic-pituitary-adrenocortical (HPA) system are characteristic of depression. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR), several studies have examined the number and/or function of GRs in depressed patients. Methods: Review scientific evidences have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR IntroductionHormones play a critical role in the development and expression of a wide range of behaviours. One aspect of the influence of hormones on behaviour is their potential contribution to the pathophysiology of psychiatric disorders and the mechanism of action of psychotropic drugs, particularly in major depression. Of all endocrine axes, the hypothalamic-pituitary-adrenal (HPA) axis has been the most widely evaluated. 1,2 The HPA axis plays a fundamental role in the response to external and internal stimuli including psychological stressors. Abnormalities in the function of the HPA axis have been described in people experiencing psychiatric disorders. Moreover, is well known the fundamental role of stress in precipitating episodes of psychiatric disorders in predisposed individuals. 1 These abnormalities seem related to changes in the ability of circulating glucocorticoids to exert their negative feedback on the secretion of HPA hormones through binding to the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) in HPA tissues. 2,3,6 In fact, previous studies have described both an impaired HPA negative feedback, leading to hypercortisolemia, as in melancholic depression. 2,6 In addition to melancholic depression, a spectrum of other conditions may be associated with increased and prolonged activation of the HPA axis, including anorexia nervosa with or without malnutrition, obsessive-compulsive disorder, panic anxiety, chronic active alcoholism, alcohol and narcotic withdrawal, excessive exercising, poorly controlled diabetes mellitus, childhood sexual abuse and hyperthyroidism. 7 Another group of states is characterized by hypoactivation of the stress system, rather than sustained activation, in which chronically reduced secretion of CRH may result in pathological hypoarousal and an enhanced HPA negative feedback. Patients with post-traumatic stress disorder, atypical, seasonal depression and the chronic fatigue syndrome fall in this category (see Table 1). Similarly, patients with fibromyalgia have decreased urinary free

Depression, sexuality and fibromyalgia syndrome: clinical findings and correlation to hematological parameters

“…It is known that cytokines such as IL-1β, TNF-α and IL-6 can trigger the inflammatory activity of FM 3,19 , and hormonal/neuronal mechanisms are probably behind this. Inflammatory mediators and cytokines can act in bone marrow and increase the production of blood cells, resulting in high hematocrit and blood hemoglobin, as observed in this study 20,21 . As well, they act in hepatocytes, altering CRP, rheumatoid factor, and complement concentrations 21,22,23 .…”

“…ACTH and cortisol levels are linked to stress, pain and depression 20 , and were altered in this sample. This could indicate an imbalance of feedback mechanisms of stress and inflammation 16,19,20,21,22 , although the activation or suppression of the hypothalamus-pituitary-adrenal axis in FM remains controversial 23,24 . Besides the activation of the hypothalamus-pituitary-adrenal axis, there are low concentrations of dehydroepiandrosterone in FM patients 25 …”

“…The pain intensity was high in patients who had a high concentration of ACTH and C3 and low concentration of immunoglobulins, which suggests a cellular immune process mediated by T cells. These are cytokine releasers that are found to be activated in FM 3,19,20,21,22,23 . The role of hormones in FM has been investigated, and the decline of sexual hormones in the climacteric syndrome could even be a potential etiology for FM 17 .…”

RU486 Reverses Emotional Disorders by Influencing Astrocytes and Endoplasmic Reticulum Stress in Chronic Restraint Stress Challenged Rats

“…Adaptation to stress is critical for maintaining physical and mental health. However, when stressors are overwhelming or are repeated over time they can eventually lead to mental illness [1, 2], and the related hypersecretion of glucocorticoids are associated with psychiatric disorders ranging from hyper emotional states to mood dysfunction [2, 3]. The amygdala is involved in the emotional value of mood and cognition, and plays a critical role in fear and anxiety-related behaviors.…”

Características endócrinas, metabólicas e indicadoras da qualidade da carne em bovinos Nelore castrados e não castrados

“…O eixo HPA controla a síntese e a liberação de glicocorticoides, mineralocorticoides e hormônios sexuais. Em situações estressantes, o eixo HPA estimula o aumento da secreção de ACTH, elevando as concentrações de cortisol circulante (JURUENA et al, 2004).…”