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

Neuroendocrine responses to psychosocial pressures have been well characterized. The defence reaction is followed by increased activity of the sympathetic nervous system. Essential hypertension might be induced by such mechanisms. The defeat reaction is characterized by increased activity along the corticotropin releasing factor-adrenocorticotropin hormone-cortisol axis, resulting in the inhibition of gonadotropin secretion. Such endocrine disturbances are followed by metabolic aberrations, and probably also by the accumulation of visceral fat. Subjects with abdominal fat accumulation (high waist/hip circumference ratio, WHR) have recently been found to exhibit a number of psychosocial handicaps, together with endocrine aberrations characteristic of the defence and, in particular, the defeat reaction, as well as the associated circulatory and metabolic aberrations. Such abnormalities, including the WHR itself, are established risk factors for cardiovascular disease and diabetes. It is postulated that increased WHR is a symptom of chronic hypothalamic arousal as a result of a defeat reaction to psychosocial pressures. This might lead to the development of disease via circulatory and metabolic derangements.
 ...
PMID:Visceral fat accumulation: the missing link between psychosocial factors and cardiovascular disease? 189 41

The risk of atherosclerosis, a leading cause of cardiovascular disease and death, is inversely related to plasma levels of high-density lipoprotein (HDL) cholesterol, although the mechanism of this protective effect is unclear. The class B scavenger receptor, SR-BI, is the first HDL receptor to be well defined at a molecular level and is a mediator of selective cholesterol uptake in vitro. It is expressed most abundantly in steroidogenic tissues, where it is coordinately regulated with steroidogenesis by adrenocorticotropic hormone (ACTH), human chorionic gonadotropin (hCG) and oestrogen, and in the liver, where its expression in rats is suppressed by oestrogen. Here we show that adenovirus-mediated, hepatic overexpression of SR-BI in mice on both sinusoidal and canalicular surfaces of hepatocytes results in the virtual disappearance of plasma HDL and a substantial increase in biliary cholesterol. SR-BI may directly mediate these effects by increasing hepatic HDL cholesterol uptake or by increasing cholesterol secretion into bile, or both. These results indicate that SR-BI may be important in hepatic HDL metabolism, in determining plasma HDL concentrations, and in controlling cholesterol concentrations in bile, and thus may influence the development and progression of atherosclerosis and gallstone disease.
 ...
PMID:Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. 916 28

The industrialized countries around the world are experiencing an epidemic of childhood obesity. The level of fatness of a child at which morbidity increases acutely and/or later in life is determined on an individual basis. Overall, however, childhood obesity substantially increases the risk of subsequent morbidity whether or not obesity persists into adulthood. The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin, the ob gene product, and the increasing knowledge of the role of neuropeptides such as pro-opiomelanocortin, neuropeptide Y and the melanocyte-concentrating hormone receptors. Environmental and exogenous factors are the main contributors to the development of a high degree of body fatness early in life. Studies involving twins suggest that approximately 50% of the tendency toward obesity is inherited. There are numerous disorders, including a number of endocrine disorders, such as Cushing's syndrome and hypothyroidism, and genetic syndromes, such as Prader-Labhard-Willi syndrome and Bardet-Biedl syndrome, that can present with obesity. A simple diagnostic algorithm allows for differentiation between primary and secondary obesity. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidemia, back pain and psychosocial problems. It is somewhat ironic that the definition of obesity in childhood is not an easy one. Direct measurements of body fat content, such as hydrodensitometry, bioimpedance, or dual-energy X-ray absorptiometry, are useful tools in scientific studies. Body mass index (BMI) is, however, now generally accepted to be a good clinical measure for the definition of obesity in children and adolescents. In preadolescent boys, BMI also relates to muscle mass and should be used for the definition of fat mass with great caution. An increased risk of death from cardiovascular disease in adults has been found in patients whose BMI had been greater than the 75th percentile as adolescents. Therapeutic strategies include psychological and family therapy, modification of lifestyle and behavior, and nutritional education. The role of regular exercise and exercise programs is emphasized, while surgical procedures and drugs used in adult obesity are still not generally recommended for obese children. Obesity is the most common chronic disorder in industrialized countries, and its impact on individual lives as well as on health economics must be recognized by physicians and the public alike. This review aims to increase awareness of the health burden and economic dimension of the epidemic of childhood obesity that is occurring around the globe.
 ...
PMID:Obesity in childhood and adolescence: clinical diagnosis and management. 1183 96

Traditionally, the role of aldosterone in heart failure was thought to be a result of its effects on epithelial cells where it induces sodium reabsorption and potassium excretion with subsequent haemodynamic effects from intravascular volume expansion. On this basis, spironolactone, a non-selective aldosterone antagonist, has been used for the treatment of congestive heart failure to block aldosterone-mediated effects in epithelial cells. The Randomized Aldactone Evaluation Study (RALES), in which spironolactone was added to existing therapy in patients with heart failure, showed a significant reduction in morbidity and mortality. These results suggest that the role of aldosterone in the pathophysiology of cardiovascular disease may be more complex than previously recognised. There now is extensive experimental and growing clinical evidence for an important physiological role for aldosterone in the pathology of cardiac and renal disease. Classical effects of aldosterone are mediated via its nuclear receptor. Novel non-epithelial effects of aldosterone are mediated via a second messenger system, which involves activation of the sodium/hydrogen antiporter. These effects of aldosterone have been demonstrated in the kidney, vascular smooth muscle cell and leukocytes, and in the regulation of rapid corticotropin suppression. It has been hypothesised that cardiac damage induced by aldosterone is independent of the presence of hypertension. In support of this, experimental evidence demonstrates that cardiovascular damage induced by aldosterone can be prevented by administration of a selective mineralocorticoid receptor antagonist. These findings suggest the dissociation between cardiovascular lesions and high blood pressure, and highlight the importance of aldosterone in the pathological changes.
 ...
PMID:Rationale for the use of aldosterone antagonists in congestive heart failure. 1192 27

Evidence from epidemiologic, clinical, and experimental studies has shown that a suboptimal intrauterine environment during early pregnancy can alter fetal growth and gestation length and is associated with an increased prevalence of adult hypertension and cardiovascular disease. It has been postulated that maternal nutrient restriction may act to reprogram the development of the pituitary-adrenal axis, resulting in excess glucocorticoid exposure and adverse health outcomes in later life. It is unknown, however, whether maternal nutrient restriction during the periconceptional period alters the development of the fetal pituitary-adrenal axis or whether the effects of periconceptional undernutrition can be reversed by the provision of an adequate level of maternal nutrition throughout the remainder of pregnancy. We have investigated the effect of restricted periconceptional nutrition (70% of control feed allowance) from 60 days before until 7 days after mating and the effect of restricted gestational nutrition from Day 8 to 147 of gestation on the development of the fetal hypothalamo-pituitary adrenal (HPA) axis in the sheep. In these studies, we have also investigated the effects of fetal number and sex on the pituitary-adrenal responses to periconceptional and gestational undernutrition. In ewes maintained on a control diet throughout the periconceptional and gestational periods, fetal plasma ACTH concentrations were higher and the prepartum surge in cortisol occurred earlier in singletons compared with twins. Plasma ACTH concentrations were also significantly higher in male compared with female singletons, and in twin fetuses, the prepartum surge in cortisol concentrations occurred earlier in males than in females. Periconceptional undernutrition resulted in higher fetal plasma concentrations of ACTH between 110 and 145 days of gestation and a significantly greater cortisol response to a bolus dose of corticotropin-releasing hormone in twin, but not singleton, fetuses in late gestation. We have therefore demonstrated that fetal number and sex each has an impact on the timing of the prepartum activation of the HPA axis in the sheep. Restriction of the level of maternal nutrition before and in the first week of a twin pregnancy results in stimulation of the fetal pituitary-adrenal axis in late gestation, and this effect is not reversed by the provision of a maintenance control diet from the second week of pregnancy.
 ...
PMID:Impact of maternal undernutrition during the periconceptional period, fetal number, and fetal sex on the development of the hypothalamo-pituitary adrenal axis in sheep during late gestation. 1196 24

Disruptions in homeostasis (ie, stress) place demands on the body that are met by the activation of 2 systems, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). Stressor-induced activation of the HPA axis and the SNS results in a series of neural and endocrine adaptations known as the "stress response" or "stress cascade." The stress cascade is responsible for allowing the body to make the necessary physiological and metabolic changes required to cope with the demands of a homeostatic challenge. Here we discuss the key elements of the HPA axis and the neuroendocrine response to stress. A challenge to homeostasis (a stressor) initiates the release of corticotropin-releasing hormone (CRH) from the hypothalamus, which in turn results in release of adrenocortiotropin hormone (ACTH) into general circulation. ACTH then acts on the adrenal cortex resulting in release of a species-specific glucocorticoid into blood. Glucocorticoids act in a negative feedback fashion to terminate the release of CRH. The body strives to maintain glucocorticoid levels within certain boundaries and interference at any level of the axis will influence the other components via feedback loops. Over- or underproduction of cortisol can result in the devastating diseases of Cushing's and Addison's, respectively, but less severe dysregulation of the HPA axis can still have adverse health consequences. These include the deposition of visceral fat as well as cardiovascular disease (eg, atherosclerosis). Thus, chronic stress with its physical and psychological ramifications remains a persistent clinical problem for which new pharmacological treatment strategies are aggressively sought. To date, treatments have been based on the existing knowledge concerning the brain areas and neurobiological substrates that subserve the stress response. Thus, the CRH blocker, antalarmin, is being investigated as a treatment for chronic stress because it prevents CRH from having its ultimate effect-a protracted release of glucocorticoids. New therapeutic strategies will depend on the discovery of novel therapeutic targets at the cellular and intracellular level. Advances in molecular biology provide the tools and new opportunities for identifying these therapeutic targets.
 ...
PMID:Neuroendocrine aspects of the response to stress. 1204 May 34

Mediators of neuroendocrine and autonomic function seem to play important roles in the core symptoms of major depression. Although centrally directed corticotropin-releasing hormones and norepinephrine contribute to core symptoms such as alterations in anxiety, arousal, and mood, they also exert significant potentially clinically relevant effects on key processes that proceed in the periphery. Thus, the core clinical manifestations of major depression may represent a fraction of a complicated systemic illness that not only influences thought and feeling, but also the processes involved in premature cardiovascular disease, osteoporosis, and premature death. Subdividing patients with major depression into meaningful biologic subgroups will facilitate the elucidation of the mechanisms that underlie the central and peripheral manifestations of major depressive illness.
 ...
PMID:Divergent endocrine abnormalities in melancholic and atypical depression: clinical and pathophysiologic implications. 1205 90

Hypertension and insulin resistance syndrome are risk factors for cardiovascular disease, and it is therefore important to identify interventions that can reduce blood pressure and improve glucose metabolism. We performed experiments aimed at determining whether intermittent fasting (IF) can improve cardiovascular health and also tested the hypothesis that beneficial effects of IF can be mimicked by dietary supplementation with 2-deoxy-D-glucose (2DG) a non-metabolizable glucose analog. Four-month-old male rats were implanted with telemetry probes to allow continuous monitoring of heart rate, blood pressure, physical activity, and body temperature. Rats were then maintained for 6 months on one of three different dietary regimens: ad libitum feeding, IF, or 2DG supplementation. Rats on the IF regimen consumed 30% less food over time and had reduced body weights compared with rats fed ad libitum, whereas rats on the 2DG regimen did not reduce their food intake and maintained their body weight. Heart rate and blood pressure were significantly decreased within 1 month in rats on IF and 2DG diets and were maintained at reduced levels thereafter. Body temperature was significantly decreased in group IF, but not in group 2DG. Levels of serum glucose and insulin were significantly decreased in rats maintained on IF and 2DG-supplemented diets, suggesting that IF and 2DG diets affect insulin sensitivity in a similar manner. Finally, rats in groups IF and 2DG exhibited increased levels of plasma adrenocorticotropin and corticosterone, indicating that these diets induced a stress response. We conclude that reductions in blood pressure, heart rate, and insulin levels, similar to or greater than those obtained with regular physical exercise programs, can be achieved by IF and by dietary supplementation with 2DG by a mechanism involving stress responses.
 ...
PMID:Intermittent fasting and dietary supplementation with 2-deoxy-D-glucose improve functional and metabolic cardiovascular risk factors in rats. 1270 4

The development of diseases in later life, such as diabetes type II, hypertension and cardiovascular disease, is linked to abnormal intrauterine conditions that reduce birth weight. Obviously, fetal development can be disturbed so profoundly, that fetal programming is changed permanently. We have examined the effects of hypoxia, or more precisely hypoxemia, on the fetal hypothalamic-pituitary-adrenal (HPA) axis and lungs using molecular biology techniques in order to elucidate the underlying mechanisms. Chronically catheterized fetal sheep were subjected to a hypoxemia (48 h) without change in arterial pH or paCO2. Major changes occurred, although the degree of hypoxemia was just moderate. There was a transient increase in the fetal plasma ACTH-concentrations with an upregulation of the cortisol-concentrations, which was more pronounced in the older, hypoxemic fetuses (134-136 days of gestation) than in the younger, hypoxemic animals (126-130 days of gestation; term is 145 days). There was an unique, differential regulation for pro-opiomelanocortin messenger RNA (mRNA), the precursor molecule of e.g. ACTH, in the pars distalis and pars intermedia of the pituitary gland. This finding supported the increased bioactivity besides the increased concentrations for ACTH. Simultaneously, there was an increase in the mRNAs of the ACTH-receptor and of the steroid-synthesizing enzymes in the fetal adrenal gland of the older, hypoxemic fetuses. No changes in the fetal plasma androstenedione-concentrations were observed. Clearly, there was a selective increase of the cortisol-synthesis. Growth and maturation of the fetal lung might also have been affected, because of the increase in surfactant-protein A mRNA in the older, hypoxemic animals and the decrease in the insulin-like growth factor-I and its binding protein-5 mRNA in the younger, hypoxemic fetuses. In summary, even a moderate degree of hypoxemia was shown to affect the different levels of fetal organism profoundly, offering a pathophysiological basis for changes in fetal development.
 ...
PMID:Fetal hypoxemia on a molecular level: adaptive changes in the hypothalamic-pituitary-adrenal (HPA) axis and the lungs. 1296 92

Obesity and high fat diets are associated with an increased prevalence of diabetes, cardiovascular disease, and hypertension. However, the mechanism(s) linking obesity and high fat diet to these metabolic and cardiovascular disorders are not fully elucidated. Leptin stimulates the formation of pro-opiomelanocortin and its products. The stimulation of the central nervous system (CNS) opioids and their receptors is associated with an increase in cardiovascular dynamics. In this study we hypothesized that obesity changed the CNS opioids and their receptors that could play a role in altered cardiovascular and autonomic nervous regulation in obesity. Male Wistar rats were fed either a high fat (HF) or regular chow (control) diet. After 12 weeks, rats were anesthetized and instrumented to record mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). A blood sample was collected and plasma glucose, insulin, leptin, beta-endorphins were measured. The brains were subsequently processed for immunohistochemistry and in situ hybridization. The HF rats were larger and had a greater percentage of body fat. Leptin and insulin levels were also higher in the HF animals. Basal MAP and RSNA were significantly higher in HF rats. Additionally, immunohistochemistry and in situ hybridization demonstrated that HF rats had increased hypothalamus mu opioid receptors compared to controls. These studies suggest that HF feeding is associated with increased body fat, plasma leptin, insulin, and hypothalamic mu opioid receptors. The increased mu opioid receptors may contribute to the higher MAP and RSNA observed in HF animals.
 ...
PMID:High fat feeding is associated with increased blood pressure, sympathetic nerve activity and hypothalamic mu opioid receptors. 1367 50


1 2 3 Next >>