Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stress system coordinates the adaptive responses of the organism to stressors of any kind.(1). The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic beta-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholaminergic input. The end-hormones of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LC/NE and beta-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5' deiodinase, which converts the relatively inactive tetraiodothyronine (T(4)) to triiodothyronine (T(3)), contributing further to the suppression of reproductive, growth and thyroid functions. They also have direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome X) and direct effects on the bone, causing "low turnover" osteoporosis. Central CRH, via glucocorticoids and catecholamines, inhibits the inflammatory reaction, while directly secreted by peripheral nerves CRH stimulates local inflammation (immune CRH). CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above. Conversely, potentiators of CRH secretion/action may be useful to treat atypical depression, postpartum depression and the fibromyalgia/chronic fatigue syndromes, all characterized by low HPA axis and LC/NE activity, fatigue, depressive symptomatology, hyperalgesia and increased immune/inflammatory responses to stimuli.
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PMID:Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. 1237 95

Stress activates the central and peripheral components of the stress system, i.e., the hypothalamic-pituitary-adrenal (HPA) axis and the arousal/sympathetic system. The principal effectors of the stress system are corticotropin-releasing hormone (CRH), arginine vasopressin, the proopiomelanocortin-derived peptides alpha-melanocyte-stimulating hormone and beta-endorphin, the glucocorticoids, and the catecholamines norepinephrine and epinephrine. Appropriate responsiveness of the stress system to stressors is a crucial prerequisite for a sense of well-being, adequate performance of tasks and positive social interactions. By contrast, inappropriate responsiveness of the stress system may impair growth and development, and may account for a number of endocrine, metabolic, autoimmune and psychiatric disorders. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors and the timing of the stressful event(s), given that prenatal life, infancy, childhood and adolescence are critical periods characterized by increased vulnerability to stressors. The developing brain undergoes rapid growth and is characterized by high turnover of neuronal connections during the prenatal and early postnatal life. These processes and, hence, brain plasticity, slow down during childhood and puberty, and plateau in young adulthood. Hormonal actions in early life, and to a much lesser extent later, can be organizational, i.e., can have effects that last for long periods of time, often for the entire life of the individual. Hormones of the stress system and sex steroids have such effects, which influence the behavior and certain physiologic functions of individuals for life. Exposure of the developing brain to severe and/or prolonged stress may result in hyperactivity/hyperreactivity of the stress system, with resultant amygdala hyperfunction (fear reaction), decreased activity of the hippocampus (defective glucocorticoid-negative feedback, cognition), and the mesocorticolimbic dopaminergic system (dysthymia, novelty-seeking, addictive behaviors), hyperactivation of the HPA axis (hypercortisolism), suppression of reproductive, growth, thyroid and immune functions, and changes in pain perception. These changes may be accompanied by abnormal childhood, adolescent and adult behaviors, including excessive fear ('inhibited child syndrome') and addictive behaviors, dysthymia and/or depression, and gradual development of components of the metabolic syndrome X, including visceral obesity and essential hypertension. Prenatal stress exerted during the period of sexual differentiation may be accompanied by impairment of this process with behavioral and/or somatic sequelae. The vulnerability of individuals to develop varying degrees and/or components of the above life-long syndrome is defined by as yet unidentified genetic factors, which account for up to 60% of the variance. CRH has marked kindling and glucocorticoids have strong consolidating properties, hence both of these hormones are crucial in development and can alone produce the above syndrome. CRH and glucocorticoids may act in synergy, as in acoustic startle, while glucocorticoids may suppress or stimulate CRH, as in the hypothalamus and amygdala, respectively. A CRH type 1 receptor antagonist, antalarmin, inhibits both the development and expression of conditioned fear in rats, and has anxiolytic properties in monkeys. Profound stressors, such as those from sexual abuse, may elicit the syndrome in older children, adolescents and adults. Most frequently, chronic dysthymia and/or depression may develop in association with gastrointestinal complaints and/or the premenstrual tension syndrome. A lesser proportion of individuals may develop the classic posttraumatic stress disorder, which is characterized by hypocortisolism and intrusive and avoidance symptoms; in younger individuals it may present as dissociative personality disorder.
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PMID:Pediatric stress: hormonal mediators and human development. 1264 70