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)

Stress-related activation of the hypothalamic-pituitary-adrenal axis (HPA) is associated with suppression of the reproductive axis. This effect has been explained by findings indicating that corticotropin-releasing hormone suppresses hypothalamic gonadotropin-releasing hormone (GnRH) secretion via an opioid peptide-mediated mechanism, and that glucocorticoids suppress both GnRH and gonadotropin secretion and inhibit testosterone and estradiol production by the testis and ovary, respectively. To evaluate whether glucocorticoids suppress the effects of estradiol on its target tissues, we examined the ability of dexamethasone to inhibit estradiol-stimulated uterine and thymic growth in ovariectomized rats. Estradiol alone, given daily for 5 days, caused dose-dependent uterine and thymic growth. Dexamethasone alone, given daily for 5 days, caused a dose-dependent decrease in body weight gain and in thymic growth. When estradiol and dexamethasone were administered simultaneously, however, body weight gain and thymic growth were also inhibited (p less than 0.05). Dexamethasone decreased estradiol-induced uterine cytosolic and nuclear estrogen receptor concentrations (E2 R0, p less than 0.05; E2nR0, respectively), but had no effect on estradiol-induced progesterone receptor concentrations (P4R0, p greater than 0.05). Levels of uterine glucocorticoid receptors were not affected by estrogen and/or dexamethasone treatment. These findings suggest that stress levels of glucocorticoids, administered over a 5-day interval, block the estradiol-stimulated growth of female sex hormone target tissues. This effect may be partially mediated by a glucocorticoid-induced decrease of the estradiol receptor concentration. Thus, another mechanism by which the HPA may influence reproductive function during stress is by a direct effect of glucocorticoids on the target tissues of sex steroids.
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PMID:Glucocorticoids inhibit estradiol-mediated uterine growth: possible role of the uterine estradiol receptor. 231 Aug 19

The influence of the POMC-system on the effects of morphine during learning are studied using physical (adrenalectomy, stress) and drug impacts (morphine, methamizol, acetysal) on the functional activity of the system. Adrenalectomized rats are found to manifest a sharp rise in the plasma and adenopituitary levels of beta-endorphin and inhibition of learning. The facilitating effect of morphine on learning (in a dose of 5 mg/kg) is inverted against the background of adrenalectomy. Dexamethasone prevents this effect, which coincides with the decrease in the beta-endorphin level. Morphine in a dose of 10 mg/kg body mass enhances learning against the background of stress applied in advance. In unstressed animals the same dose of morphine results in sharp deterioration of learning. Naloxone prevents the positive effect of morphine under stress. The dose-dependent opposite effects of morphine on the processes of learning are assumed to be modulated by the changes taking place in the ratio of the opioid/antiopioid POMC-derivatives under functional and drug influences.
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PMID:Participation of the POMC-system in the effects of morphine on the avoidance reaction in albino rats. 239 49

This paper observed the effect of Dexamethasone (Dex) on the levels of plasma Beta-endorphin-like-immunoreactivity (ir-beta-EP) and its correlation with hemodynamics during the shock. Ten adult mongrel dogs were randomized into two groups. Intestinal shock was created by occluding both superior mesenteric artery and vein in the two groups. After two hours of occlusion, the dogs in treated group were given Dex (5 mg/kg) and the dogs in control group were given normal saline. The intestinal vascular obstruction was released four hours later. It was shown that plasma levels of ir-beta-EP in control group were increased significantly during the shock and correlated significantly with deteriorated hemodynamics. In Dex treated group, the levels of plasma ir-beta-EP and ACTH were significantly lower than that in control group, hemodynamics were improved, and the survival times were much longer. Our results suggest that endogenous opiate beta-EP is involved in the cardiovascular pathophysiology of intestinal shock, and the beneficial effects of steroids (Dex) in the treatment of shock are correlated with its suppressing endogenous beta-EP secretion and release.
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PMID:[Effect of dexamethasone on the levels of plasma beta-endorphin-like-immunoreactivity in intestinal ischemia shock in the dog]. 253 24

Vasopressin infusion has been shown to decrease plasma adrenocorticotropic hormone (ACTH) concentration and transiently increase plasma cortisol concentration in conscious dogs. In the present study, one experiment tested the hypothesis that vasopressin infusion decreases ACTH by activation of a V1 receptor mechanism, e.g., by increasing atrial pressures and stimulating the low-pressure baroreceptor reflex. Administration of a vasopressin V1 antagonist eliminated the increases in atrial pressure and decreases in heart rate with vasopressin infusion (1 ng.kg-1.min-1), as it eliminated the decrease in ACTH, which is consistent with baroreflex-mediated inhibition of ACTH by vasopressin. A second experiment evaluated the role of ACTH in the increase in glucocorticoids. Dexamethasone pretreatment, which inhibits ACTH secretion, abolished the increase in glucocorticoid concentration with vasopressin infusion, indicating that ACTH is necessary for the glucocorticoid response. A third experiment was performed to determine whether the glucocorticoid response could be restored in dexamethasone-treated dogs, when ACTH concentration was maintained near control levels by intravenous infusion of synthetic alpha-ACTH-(1-24) (0.3 ng.kg-1.min-1). In these dogs, vasopressin infusion produced a sustained increase in plasma glucocorticoid concentration from 22 +/- 3 to 49 +/- 8 ng/ml (P less than 0.001). Infusing higher levels of ACTH (0.5 ng.kg-1.min-1) enhanced basal glucocorticoid levels but did not enhance the response to vasopressin. Vasopressin infusion did not alter clearance of glucocorticoids. Collectively, these results suggest that vasopressin directly stimulates adrenal glucocorticoid production, provided that background levels of ACTH are present.
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PMID:Vasopressin: a regulator of adrenal glucocorticoid production? 253 36

We have developed a "sandwich"-type immunoradiometric assay for corticotropin (ACTH), with a detection limit of 2 ng/L. Two antibodies are used: a mouse monoclonal antibody directed against ACTH[1-17] and labeled with 125I; and a purified polyclonal goat antibody directed against ACTH[34-39] and conjugated to biotin. We could separate 125I-labeled antibody bound to ACTH from 125I-labeled antibody not bound to ACTH by using an avidin-biotin bridge, with avidin bound to a polystyrene ball. This assay reacts with ACTH[1-39] but shows no reaction with ACTH fragments [1-24], [1-17], or [34-39], or with melanotropin, endorphins, or lipotropin. This assay is sensitive enough to detect ACTH in plasma of all normal adults. Concentrations measured in 94 adults between 0800 and 1000 hours were normally distributed on a log scale, with a mean of 19.5 ng/L and a 95% range of 7.1 to 53.8 ng/L. Dexamethasone given at 2300 hours to 14 adults suppressed ACTH to less than 4 ng/L in 13 of the subjects and to 8 ng/L in the 14th. Metyrapone given to 13 adults at 2300 hours increased ACTH to 245.3 ng/L (95% range, 90.1 to 667.7 ng/L). This assay accurately classified patients with disorders of the adrenal system.
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PMID:Immunoradiometric assay of corticotropin with use of avidin-biotin separation. 254 49

We have developed a redox system for brain-enhanced delivery of dexamethasone based on an interconvertible dihydropyridine in equilibrium pyridinium salt carrier. Dexamethasone, when combined with the lipoidal carrier, readily crosses the blood-brain barrier. The carrier, when oxidized, reduces its rate of exit from the brain. The aim of the study was to evaluate the capacity of a dexamethasone-chemical delivery system (DX-CDS) and dexamethasone (DEX) to suppress stress-induced elevations of plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Adult male Sprague-Dawley (CD) rats were administered either DX-CDS (10 mg/kg), an equimolar dose of DEX or the drug vehicle (2-hydroxypropyl-beta-cyclodextrin) by a single tail vein injection. Rats then received either no stress or a restraint stress for a 5- or 15-min duration on days 1, 3, 5 or 7 after drug administration and trunk blood was rapidly collected. To assess peripheral effects of DX-CDS and DEX, 1 ml of blood was removed via orbital puncture and evaluated for total and differential leukocyte counts in a separate group of animals. Both DX-CDS and DEX were effective on day 1 in suppressing, by greater than 95%, ACTH secretion induced by a 5-min stress. However, DX-CDS was effective through day 5 (44% suppression) while DEX was not effective after 24 h. When 15 min of stress was applied, DX-CDS effected a significant ACTH suppression through 7 days while DEX was effective for only 3 days. DX-CDS was effective through day 7 (55%) in suppressing CORT after a 15-min stress while DEX was effective for 3 days only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for prolonged suppression of stress-induced release of adrenocorticotropic hormone and corticosterone with a brain-enhanced dexamethasone-redox delivery system. 254 77

Adult male albino rats underwent chronic treatment with synthetic adrenocorticotropin and Dexamethasone, and were examined for a long time after the administration of these drugs. The major salivary glands were observed by means of histological and histochemical methods. We did not find enzymatic modifications whereas morphological damage was particularly evident in the submaxillary and parotid glands, especially all after Dexamethasone treatment; this damage is to be found up to at least 14 days after the end of treatment.
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PMID:Morphofunctional research on the effects of steroid-stimulating and -inhibiting drugs on the major salivary glands of rats. 254 42

In addition to prolonged glucocorticoid therapy (not discussed here), at least five other conditions cause Cushing's syndrome. They are excessive corticotropin secretion by the pituitary gland (which results in Cushing's disease), ectopic production of corticotropin by malignant nonpituitary tumors, benign adrenal adenoma, adrenal carcinoma, and primary adrenocortical nodular dysplasia. Each can be distinguished by a specific pathophysiologic process that triggers the adrenal glands to overproduce glucocorticoids. At present, diagnosis of Cushing's syndrome or disease relies heavily on the dexamethasone (Decadron, Hexadrol) suppression test. After diagnosis, other studies, including computed tomography, magnetic resonance imaging, and corticotropin radioimmunoassay, can be used to localize the site of the lesion. Treatment, of course, depends on the underlying cause.
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PMID:Cushing's syndrome. How to pinpoint and treat the underlying cause. 255

In humans, the syndrome of cortisol resistance is characterized by the absence of signs and symptoms of Cushing's syndrome, elevated total and unbound plasma cortisol concentrations, and increases in urinary free cortisol excretion and plasma adrenocorticotropic hormone. In one family, a severely affected member had hypertension and hypokalemic alkalosis associated with increased plasma concentrations of corticosterone and deoxycorticosterone. These patients are resistant to suppression of the pituitary-adrenal axis by dexamethasone. Dexamethasone therapy, however, effectively corrected hypertension and hypokalemic alkalosis in the severely affected patient, without causing signs of glucocorticoid excess. The glucocorticoid receptor from these patients has a low affinity for glucocorticoids and is unstable during thermal activation. Both the molecular weight of the glucocorticoid receptor and the size of the corresponding mRNA are similar to those of normal controls. Transformation of B-lymphocytes with Epstein-Barr virus leads to induction of glucocorticoid receptors. Receptor induction, however, is lower in patient cells than those obtained from normal controls. This decreased induction parallels decreased expression of glucocorticoid receptor mRNA. Thus, in this form of glucocorticoid resistance the glucocorticoid receptor is abnormal and leads to diminished target organ responsiveness. Many New World primates exhibit glucocorticoid "resistance," without apparent pathology. These species have markedly elevated plasma cortisol, both total and unbound concentrations, increased urinary free cortisol excretion, and marked increases in plasma adrenocorticotropic hormone and beta-endorphin. The glucocorticoid receptors of these primates have decreased affinity for glucocorticoids, are thermolabile, and are not induced by Epstein-Barr virus transformation as indicated by specific binding and mRNA expression. Both the molecular weight of the glucocorticoid receptor and the size of the corresponding mRNA are similar to those of normal controls. Despite the high plasma cortisol concentrations in these primates, there is no sodium retention and aldosterone levels are actually increased. The kidney aldosterone receptor cross-reacts poorly with cortisol, explaining the absence of sodium retention. New World primates also have progesterone, estrogen, aldosterone, and vitamin D insensitivity, suggesting a common factor linking steroid hormone receptors.
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PMID:Glucocorticoid resistance in humans and nonhuman primates. 264 36

Different hormones of the hypothalamo-pituitary-adrenal axis (corticotropin-releasing factor, adrenocorticotropic hormone, corticosterone) were measured in brain pieces (stalk, median eminence, hypothalamus), hypophyses, adrenals and plasma of 21-day-old rat fetuses from mothers which were given either plain tap water or water containing dexamethasone acetate (10 micrograms/ml) from day 15 to 21 of gestation. Dexamethasone induced drastic reduction of body weight (-66% vs. controls), severe atrophy of the adrenals (-83%) and a sharp drop in their corticosterone content (-74%). Fetal plasma corticosterone levels were below the lower limit of detection of the competitive corticosteroid-binding globulin (CBG) radioassay (less than 0.01 microgram/ml). Both atrophy and severe reduction of the adrenal activity in fetuses from dexamethasone-treated females were in good correlation with a drastic decrease in plasma adrenocorticotropic hormone (ACTH) levels which were below the lower limit of detection of the radioimmunoassay (RIA) used (less than 10 pg/ml) and a significant reduction in pituitary ACTH content (-93%). The low corticostimulating activity of the fetal hypophyses was associated with a drop in both corticotropin-releasing factor (CRF) hypothalamic content (-57%) and concentration (-67%). The effects of dexamethasone on plasma and pituitary ACTH concentrations in 21-day-old fetuses were compared to those, previously reported, of encephalectomy and decapitation performed on day 16 of gestation. The reported data were consistent with the present results, suggesting both pituitary and hypothalamic sites for the in vivo inhibiting action of dexamethasone on the rat hypothalamic-pituitary-adrenal axis in late gestation.
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PMID:Effects of chronic maternal dexamethasone treatment on the hormones of the hypothalamo-pituitary-adrenal axis in the rat fetus. 282 15


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