UNIPROT:P01189 - FACTA Search

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Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin converting enzyme (ACE) inhibitor therapy in conjunction with loop diuretics and, possibly, digoxin, is associated with a relatively high incidence of recurrent heart failure and death. Even high doses of ACE inhibitors may not completely suppress the renin-angiotensin-aldosterone system; aldosterone "escape' may occur through non-angiotensin II dependent mechanisms involving corticotropin, atrial natriuretic peptide, serum potassium, and deficient high-density lipoprotein cholesterol concentrations. Addition of spironolactone (an aldosterone receptor blocker) to an ACE inhibitor regimen causes marked diuresis and symptomatic improvement. The Randomized Aldactone Evaluation Study (RALES) was organized to explore the role of combination therapy with spironolactone in patients with heart failure. Patients with New York Heart Association Functional Class II-IV heart failure and left ventricular ejection fractions < or = 40% who were on regimens comprising an ACE inhibitor, loop diuretic, and, possibly, digoxin were randomized to receive placebo or spironolactone in doses of 12.5, 25, 50, or 75 mg per day. Eve at the lowest dose of spironolactone, a significant decrease in plasma N-terminal pro-atrial natriuretic peptide occurred, with concomitant increase in concentrations of plasma renin and urinary aldosterone. As prophylaxis for heart failure, a daily dose of 25 mg of spironolactone and monitoring of serum potassium concentrations are recommended; symptomatic therapy in refractory or severe heart failure may require doses as high as 100 mg b.i.d. The RALES Mortality Trial will follow up 1400 similar patients for 3 years to determine the effect of the addition of spironolactone on combined mortality and hospitalization for heart failure.
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PMID:ACE inhibitor co-therapy in patients with heart failure: rationale for the Randomized Aldactone Evaluation Study (RALES). 868 55

The effects of chronic stress on the hypothalamic-pituaitary-adrenocortical (HPA) axis were studied in five inbred rat strains, i.e. Brown Norway (BN), Fischer (FIS), Lewis (LEW), Spontaneously Hypertensive (SHR) and Wistar Kyoto (WKY). Previously, these rat strains had been shown to display clear behavioral differences in the forced swimming test that presumably measures depression-like behavior, BN and WKY being more passive than the other strains. Here we test the hypothesis that the differences in behavioral immobility might be associated with an abnormal HPA response to chronic immobilization (IMO) stress. In stressnaive rats under basal conditions (morning) there were no differences among strains in adrenal weight, serum adrenocorticotropin hormone (ACTH) and corticosterone (B) levels, cortictropin-releasing factor (CRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and hippocampal glucocorticoid and mineralocorticoid receptor (GR and MR) mRNA. After chronic IMO, basal serum ACTH levels were increased in LEW, SHR and WKY, but not in BN or FIS rats, whereas basal B levels were increased in BN, FIS, SHR and WKY rats, but not in LEW. The increase in adrenal weight was also strain dependent and correlated negatively with chronic IMO-induced hypercorticosteronemia. These peripheral differences among strains were not observed at central levels. Thus, chronic IMO increased the CRF mRNA content in the PVN, analyzed by in situ hybridization, similarly in all strains. In addition, after chronic IMO no differences were found among strains in hippocampal GR mRNA and RM mRNA contents. Considering data from all strains together, chronic IMO reduced the GR mRNA (50-60%) content in the hippocampal CA1, CA3 and DG areas, and slightly diminished (11-13%) MR mRNA levels in CA1 and CA3 areas. The present results indicate that: (i) chronic IMO down-regulates GR mRNA in the hippocampus and slightly up-regulates CRF mRNA in the hypothalamic PVN similarly in all strains; (ii) after chronic IMO interstrain differences were observed in serum ACTH and B levels as well as adrenal hypertrophy; (iii) some changes are probably located at the adrenal level since changes in serum B level and adrenal weight were not related to changes in ACTH; (iv) in LEW and WKY rats, B hyporesponsiveness to chronic IMO might be linked to low adrenal sensitivity to ACTH, and (v) HPA axis changes induced by the chronic IMO procedure are not related to previously reported data on depressive-like behavior of BN and WKY in the forced swimming test.
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PMID:Hypothalamic-pituitary-adrenal response to chronic stress in five inbred rat strains: differential responses are mainly located at the adrenocortical level. 873 88

In gonadectomized (GDX) animals replaced with subcutaneous steroid implants supplying physiological levels of testosterone (T; 1-10 ng/ml), the magnitude of adrenocorticotropic hormone (ACTH) and corticosterone (B) responses to restraint was negatively correlated with the level of T replacement, reflecting the inhibitory influence of T on hypothalamic-pituitary-adrenal (HPA) responses to stress. Although T had no effect on resting-state levels of corticotropin-releasing hormone (CRH) in the median eminence, arginine vasopressin (AVP) levels were significantly lower in GDX animals replaced with higher T levels, and the magnitude of the ACTH response to restraint was strongly correlated with median eminence levels of AVP. High physiological levels of T increased glucocorticoid receptor binding in the medial preoptic area (MPOA), with no effect on mineralocorticoid receptor binding or on glucocorticoid receptor binding in other regions. Crystalline T or B implants in the MPOA significantly reduced plasma ACTH and B responses to 10 min of restraint stress compared with cholesterol-implanted controls. Moreover, B or T MPOA implants also decreased resting-state levels of AVP but not CRH in the median eminence, and these effects were correlated with ACTH responses to restraint. Finally, lesioning the MPOA blocked the inhibitory effects of high peripheral T levels on ACTH and B responses to restraint. Thus, variations in the magnitude of HPA responses to stress among males are explained in part by individual differences in circulating T levels, and the MPOA is a critical site for this effect via the inhibition of hypophysial AVP.
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PMID:The inhibitory effect of testosterone on hypothalamic-pituitary-adrenal responses to stress is mediated by the medial preoptic area. 877 55

Brief periods of hypoxia during labour and birth are a frequent occurrence. Within the CNS, the hippocampus is known to be particularly vulnerable to the damaging effects of hypoxia/ischaemia in both adult and immature animals. The hippocampus also contains the highest concentration of corticosteroid receptors of any brain region and both mineralocorticoid (type I) receptors and glucocorticoid (type II) receptors in the hippocampus play a role in the regulation of basal diurnal and stress-induced glucocorticoid secretion. Given this background, the aim of this study was to test whether an acute period of anoxia during the birth process may have lasting effects on CNS corticosteroid receptor levels and/or pituitary-adrenocortical function. Type I and type II corticosteroid receptor binding sites in the hippocampus and hypothalamus were compared in adult rats that had been born vaginally, born by a Caesarean procedure or born by a Caesarean procedure with 5, 10 or 15 min of added anoxia. Using 14 nM [3H]corticosterone as radioligand, mineralocorticoid receptor binding was reduced by approximately 50% in the hippocampus and hypothalamus of adult rats that had been born by the Caesarean procedure either with or without an added period of anoxia, in comparison to vaginally born controls. Saturation analysis revealed that these reductions resulted from decreases in affinity of the mineralocorticoid receptor for [3H]corticosterone, with no change in numbers of receptors. Birth condition had no effect on glucocorticoid receptor binding capacities in the hippocampus or hypothalamus. A small increase in basal corticosterone secretion during the diurnal trough was observed in adult animals that had been born by Caesarean section with 5 or 15 min of added anoxia. The plasma corticosterone response to a 20-min restraint stress was reduced in adult animals born by Caesarean section with or without an added period of anoxia, in comparison to vaginally born controls. However the adrenocorticotropin response to stress was largely unaffected by birth condition. The results indicate that an acute birth insult is sufficient to produce long-lasting alterations in hippocampal and hypothalamic mineralocorticoid receptor sites, accompanied by changes in basal and stress-induced glucocorticoid secretion.
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PMID:Hippocampal and hypothalamic type I corticosteroid receptor affinities are reduced in adult rats born by a caesarean procedure with or without an added period of anoxia. 881 63

Aldosterone, the most important mineralocorticoid, regulates electrolyte excretion and intravascular volume mainly through its effects on renal distal convoluted tubules and cortical collecting ducts. Excess secretion of aldosterone or other mineralocorticoids or abnormal sensitivity to mineralocorticoids may result in hypertension, suppressed plasma renin activity, and hypokalemia. Such conditions often have a genetic basis, and studies of these conditions have provided valuable insights into the normal and abnormal physiology of mineralocorticoid action. Deficiencies of steroid 11 beta-hydroxylase or 17 alpha-hydroxylase are types of congenital adrenal hyperplasia, the autosomal recessive inability to synthesize cortisol. These two defects often cause hypertension because of overproduction of cortisol precursors that are, or are metabolized to, mineralocorticoid agonists. These disorders result from mutations in the CYP11B1 and CYP17 genes encoding the corresponding enzymes. Glucocorticoid-suppressible hyperaldosteronism is an autosomal dominant form of hypertension in which aldosterone secretion is abnormally regulated by corticotropin. It is caused by recombinations between linked genes encoding closely related isozymes, 11 beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2), generating a dysregulated chimeric gene with aldosterone synthase activity. Apparent mineralocorticoid excess is a loss of functional ligand specificity of the mineralocorticoid receptor caused by a deficiency of the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase, an enzyme that normally metabolizes cortisol to cortisone to prevent cortisol from occupying the receptor. This autosomal recessive form of severe hypertension results from mutations in the HSD11K (HSD11B2) gene.
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PMID:Inherited forms of mineralocorticoid hypertension. 895 79

Recently, fibromyalgia (FMS) was shown to be a disorder associated with an altered functioning of the stress response system. FMS patients display a hyperreactive pituitary adrenocorticotropic hormone (ACTH) release in response to corticotropin-releasing hormone (CRH) and to insulin-induced hypoglycemia. We suggested that negative feedback of cortisol could be deranged. Therefore we investigated the properties and function of the glucocorticoid receptors (GR) in FMS patients and compared the results with those of healthy persons and patients with chronic low back pain (LBP a localized pain condition). Forty primary FMS patients (F:M = 36:4), 28 LBP patients (25:3) and 14 (12:2) healthy, sedentary control persons were recruited for the study. Urinary free cortisol excretion in FMS and LBP patients was lower compared to controls. Only FMS patients displayed lower CBG and basal serum cortisol concentrations when compared to controls. However, plasma free cortisol concentrations were similar in the three groups. There was no difference in the number of GR per cell among the three groups (FMS: 6498 +/- 252, LBP: 6625 +/- 284, controls: 6576 +/- 304), but the dissociation constant (Kd) of the FMS (14.5 +/- 0.9 nmol/l) and LBP (14.7 +/- 1.3 nmol/l) subjects was significantly higher than that of the controls (10.9 +/- 0.8 nmol/l) (p < .05). The maximal stimulation of the lymphocytes, as measured by the maximal thymidine incorporation (in the absence of cortisol) in the FMS group was approximately 1.5 times higher (p < .05) than in the control or LBP group. The ED50 (the cortisol concentration giving 50% inhibition of the thymidine incorporation), however, was identical in all three groups. We conclude that FMS patients have a mild hypocortisolemia, increased cortisol feedback resistance in combination probably with a reduced CRH synthesis or release in the hypothalamus. The role of the GR and mineralocorticoid receptor (MR) in the CRH regulation in the FMS patients remains to be solved.
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PMID:Glucocorticoid receptors, fibromyalgia and low back pain. 948 5

After 24 hr of maternal deprivation, significant elevations in ACTH and the naturally occurring glucocorticoid corticosterone (CORT) are observed during the stress-hyporesponsive period. The deprived pups also showed in the paraventricular nucleus (PVN) a marked increase of stress-induced c-fos mRNA and a reduction of corticotropin-releasing hormone (CRH) and glucocorticoid receptor (GR) mRNA; in hippocampal CA1, a reduction of the mineralocorticoid receptor (MR) and GR was observed. Here, we examined whether these changes are reversed by (1) preventing the elevations of CORT characteristic for the 11-d-old deprived pups by administering the synthetic glucocorticoid dexamethasone (DEX); or (2) reinstating some aspects of maternal behavior. The pups were either (1) left undisturbed, (2) stroked, or (3) stroked and episodically fed by cheek cannulation. At postnatal day 12, peripheral and neural stress markers were measured. Nondeprived animals served as controls. Experiment 1 demonstrates that although CORT was kept low by DEX, the central effects on CORT receptors, CRH, and c-fos mRNA were still present, except for MR in hippocampal CA1. Experiment 2 shows that stroking alone prevented the stress-induced rise in ACTH and c-fos mRNA and in the reduction in CRH and MR mRNA. In pups that were fed and stroked, CORT and GR mRNA resembled nondeprived controls. In conclusion, the changes in peripheral endocrine responses and in the brain cannot be attributed to the effect of elevated CORT concentrations, which are characteristic of the maternally deprived neonate. However, reinstating some components of the dams' nurturing behavior can reverse the effects evoked by maternal deprivation.
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PMID:Maternal deprivation effect on the infant's neural stress markers is reversed by tactile stimulation and feeding but not by suppressing corticosterone. 982 70

A dose of dexamethasone was determined in rats (50 micrograms/kg s.c.) that suppressed the corticosterone response to restraint stress by 80%. Corticosteroid receptor occupancy estimates found that the 50 micrograms/kg s.c. dose of dexamethasone had no significant effect on available glucocorticoid receptor (GR) or mineralocorticoid receptor (MR) binding in brain regions (hypothalamus, hippocampus and cortex); on the other hand dexamethasone produced a selective and significant decrease in available GR in peripheral tissues (pituitary and spleen). Functional studies showed that the 50 micrograms/kg s.c. dose of dexamethasone completely blocked the effects of corticotropin-releasing hormone (CRH; 0.3-3.0 micrograms/kg i.p.) on corticosterone secretion, but did not inhibit the corticosterone response to an adrenocorticotropin hormone (ACTH; 2.5 I.U./kg i.p.) challenge. These studies indicate that this dose of dexamethasone exerts its inhibitory effects on the HPA axis primarily by acting at GR in the pituitary. The plasma dexamethasone levels produced by this dose of dexamethasone are similar to those present in humans the afternoon after an oral dexamethasone suppression test (DST), a time at which many depressed patients escape from dexamethasone suppression. These results support and extend other studies which suggest that the DST provides a direct test of the effects of increased GR activation in the pituitary on ACTH and cortisol secretion.
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PMID:Dexamethasone suppression of corticosteroid secretion: evaluation of the site of action by receptor measures and functional studies. 1067 79

Glucocorticoids may underlie the association between prenatal stress, low birth weight and adult stress-associated disorders, e.g. hypertension and type 2 diabetes, increased hypothalamic-pituitary-adrenal (HPA) activity and affective dysfunction. Normally, 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) rapidly inactivates glucocorticoids in placenta and many foetal tissues, thus acting as a 'barrier' to maternal steroids. We investigated the effect of inhibiting foeto-placental 11beta-HSD in rats, using carbenoxolone (CBX), on subsequent HPA activity and regulation and stress-induced behaviour in adult offspring. Pregnant Wistar rats were injected with CBX (12.5 mg s.c.) or vehicle daily throughout pregnancy. CBX treatment reduced birth weight. Adult offspring of CBX-treated dams had persistently reduced body weight, increased basal corticosterone (CORT) levels, increased corticotropin-releasing hormone (CRH) and reduced glucocorticoid receptor (GR) mRNA in the hypothalamic paraventricular nucleus, though hippocampal GR and mineralocorticoid receptor (MR) mRNA expression were unaltered. In addition, these animals showed less grooming and rearing in an open field and reduced immobility in a forced swim test, and had increased GR mRNA expression in the basolateral (BLA), central (CEA) and medial (MEA) nuclei of the amygdala, with unaltered MR mRNA. These data suggest that disturbance of the foeto-placental enzymatic barrier to maternal glucocorticoids reduces birth and body weight, and produces permanent alterations of the HPA axis and anxiety-like behaviour in aversive situations. The behavioural and HPA effects may reflect GR gene programming in amygdala and hypothalamus, respectively. Foetal overexposure to endogenous glucocorticoids (prenatal stress or reduced activity of foeto-placental 11beta-HSD) may represent a common link between the prenatal environment, foetal growth and adult neuroendocrine and affective disorders.
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PMID:Inhibition of 11beta-hydroxysteroid dehydrogenase, the foeto-placental barrier to maternal glucocorticoids, permanently programs amygdala GR mRNA expression and anxiety-like behaviour in the offspring. 1076 36

The hypothalamic-pituitary-adrenal axis is hyporesponsive to stress in late pregnancy, exemplified as reduced adrenocorticotropic hormone (ACTH) and corticosterone responses to restraint, but the mechanisms are unknown. We investigated forward drive and negative feedback upon the hypothalamic-pituitary-adrenal axis in pregnant rats. Corticotropin-releasing hormone (CRH) and vasopressin mRNA expression in the parvocellular paraventricular nucleus and mineralocorticoid and glucocorticoid receptor expression in the paraventricular nucleus and hippocampus were quantified with in situ hybridization. Because it can enhance the corticosterone negative feedback signal, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) bioactivity in these brain regions and anterior pituitary was measured in vitro, and ACTH and corticosterone stress responses were measured after intracerebroventricular glycyrrhetinic acid, an 11beta-HSD inhibitor. Changes in corticosterone feedback on ACTH secretion were examined after pharmacological adrenalectomy by metyrapone and aminoglutethimide. Parvocellular paraventricular nucleus CRH mRNA content was reduced on day 21 and the CRH mRNA : vasopressin mRNA ratio was unaltered, indicating decreased production of both CRH and vasopressin. An increase in glucocorticoid receptor mRNA expression in the dentate gyrus (mineralocorticoid receptor mRNA expression was unaltered) and increased 11beta-HSD1 activity in the paraventricular nucleus and anterior pituitary suggest an increase in slow negative feedback mechanisms in pregnancy, but glycyrrhetinic acid did not modify the stress response. After metyrapone/aminoglutethimide treatment, corticosterone decreased ACTH secretion more slowly in pregnancy, indicating a decrease in rapid feedback sensitivity. Thus, reduced forward drive rather than increased effectiveness of glucocorticoid negative feedback may underlie stress hyporesponsiveness of the hypothalamic-pituitary-adrenal axis in pregnancy.
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PMID:Attenuation of hypothalamic-pituitary-adrenal axis stress responses in late pregnancy: changes in feedforward and feedback mechanisms. 1092 94

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