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)

Carbamazepine, a tricyclic anticonvulsant with chemical resemblance to imipramine, has been recently successfully introduced as a prophylactic agent and acute treatment modality for manic-depressive illness (Ballenger and Post 1980; Okuma 1983; Post et al. 1984). The interest in carbamazepine emerges from its ability to dampen paroxysmal neuronal activity not only in epilepsy, but also in those particular systems that appear to be involved in the etiology of episodic affective illness (Post et al. 1983). These affective episodes are frequently associated with endocrine irregularities of the hypothalamic-pituitary-adrenocortical (HPA) axis, including increased cortisol secretion (Halbreich et al. 1985), nonsuppression of corticosteroids following dexamethasone, and blunted corticotropin (ACTH) release after stimulation with human corticotropin-releasing hormone (h-CRH) (Holsboer et al. 1986, 1987) or its heterologous ovine analog (Gold et al. 1986). Some recent reports have shown that carbamazepine treatment may interfere with HPA physiology, as it induces Dexamethasone Suppression Test (DST) nonsuppression (Privitera et al. 1982; Rubinow et al. 1984) and enhances mean urinary free cortisol secretion (Rubinow et al. 1986). To further explore the pathophysiology of this phenomenon of an altered HPA function, we conducted h-CRH tests in six patients in stable remission from major depression during long-term carbamazepine treatment to look for possibly drug-induced modulations. In two of six patients, we observed highly abnormal ACTH responses.
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PMID:Exaggerated corticotrophic cell response to human corticotropin-releasing hormone in two patients during long-term carbamazepine treatment. 284 Sep 79

Dogs with spontaneous pituitary-dependent hyperadrenocorticism were divided into two groups, one with normal plasma concentrations of alpha-MSH (normal alpha-MSH dogs, n = 26) and the other with high plasma concentrations of alpha-MSH (high alpha-MSH dogs, n = 14), on the presumption that high alpha-MSH concentrations indicated a parent cell of pars intermedia origin. The urinary corticoid/creatinine ratios of the high alpha-MSH dogs were significantly higher than those of the normal alpha-MSH dogs. The percentage decrease of the corticoid/creatinine ratios following dexamethasone administration was significantly higher in the normal alpha-MSH dogs than in the high alpha-MSH dogs. Dexamethasone resistance occurred in both the normal alpha-MSH dogs (4 out of 26) and the high alpha-MSH dogs (7 out of 14), indicating a relative rather than an absolute difference. The short-term effect of orally administered bromocriptine, at a dose (10 micrograms/kg body weight) known to be effective in lowering prolactin concentrations in dogs, was investigated by measuring concentrations of cortisol, ACTH and alpha-MSH in plasma at 4, 6 and 8 h after administration. Significant decreases were observed for cortisol in both groups and for alpha-MSH only in the high alpha-MSH dogs. The effect of 5 days of bromocriptine administration (10 micrograms at 12-h intervals) was assessed by measurements of urinary corticoid/creatinine ratios. Considering both groups as a whole, only the corticoid/creatinine ratios of the high alpha-MSH dogs decreased significantly on the first day of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of bromocriptine on corticotrophin, melanotrophin and corticosteroid secretion in dogs with pituitary-dependent hyperadrenocorticism. 284 49

The present studies were undertaken to further assess the role of plasma beta-endorphin (beta-EP) in the hyperphagia induced by the glucose antimetabolite, 2-deoxy-D-glucose (2-DG). Plasma concentrations of immunoreactive beta-EP (ir-beta-EP) were measured at the end of the first hour of feeding in all animals treated with 400 mg/kg 2-DG. Previous studies had shown a consistent, positive association between 2-DG hyperphagia and plasma ir-beta-EP concentrations, but the present data revealed dissociations between hyperphagia and plasma ir-beta-EP. Dexamethasone administration blocked the 2-DG-induced rise in plasma ir-beta-EP, but had no effect on the 2-DG hyperphagia measured at 1 hour. Forced drinking of a 2% NaCl solution decreased 2-DG hyperphagia, but not the 2-DG induced rise in plasma ir-beta-EP. Thus, elevations in plasma ir-beta-EP are not necessary for the full expression of 2-DG-induced hyperphagia in dexamethasone-treated rats. Furthermore, decreased feeding responses to 2-DG could coexist with increased levels of plasma ir-beta-EP in NaCl-treated normal rats. Elevations in plasma ir-beta-EP do not appear to be the critical opiate link in 2-DG induced hyperphagia.
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PMID:Experimental dissociation of food intake and plasma beta-endorphin following 2-deoxy-D-glucose in rats. 293 39

We have investigated the role of adrenal steroids and the opiates in regulating arginine vasopressin (AVP) secretion into the pituitary stalk blood of the rat. The portal plasma concentration of AVP in urethane-anesthetized male rats was 532 +/- 68 pg/ml (mean +/- SEM), while the peripheral plasma AVP concentration in intact urethane-anesthetized rats was 20.7 +/- 5.7 pg/ml. Column chromatography on Sephadex G-25 of an extract of a pool of portal plasma revealed that the material being assayed comigrated with synthetic AVP. Bilateral adrenalectomy (ADX) 5 days before the collection of portal blood elevated portal plasma AVP concentrations approximately 6-fold (655 +/- 124 pg/ml in controls vs. 4090 +/- 504 pg/ml in adrenalectomized animals). Dexamethasone administration (15 micrograms/kg X day) for 5 days prevented the ADX-induced increase in portal plasma AVP concentrations without significantly changing portal plasma AVP concentrations in intact rats. Portal plasma concentrations of beta-endorphin were not changed by ADX or dexamethasone treatment. The iv infusion of morphine sulfate (3 mg/kg) dramatically decreased the concentration of AVP in the portal plasma of the rat (501 +/- 101 pg/ml before morphine vs. 185 +/- 50 pg/ml after morphine). The inhibitory effect of morphine was reversed by naltrexone (1.0 mg/kg), whereas naltrexone alone did not alter AVP secretion. Morphine administration also decreased systemic plasma AVP concentrations in urethane-anesthetized rats (27.1 +/- 6.6 pg/ml in controls vs. 3.3 +/- 1.3 pg/ml in morphine-treated rats). Naltrexone treatment reversed this effect. These results suggest that AVP secretion into pituitary stalk blood is under the inhibitory influence of the adrenal steroids, and the increased concentration of AVP found in portal blood may be partially responsible for the elevated levels of ACTH after ADX. Furthermore, morphine-induced activation of the pituitary-adrenal axis is apparently independent of hypothalamic AVP secretion.
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PMID:The concentration of arginine vasopressin in pituitary stalk plasma of the rat after adrenalectomy or morphine. 293 37

The hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in many patients with depression, probably at all levels of the axis. To determine if HPA dysregulation is associated with severity of depression, we studied a group of 66 patients with major depressive disorder. Each patient underwent a pretreatment Dexamethasone Suppression Test, with plasma postdexamethasone cortisol determination at 8:00 AM, 4:00 PM, and 11:00 PM. All three postdexamethasone cortisol levels were significantly correlated with the Hamilton Rating Scale for Depression (HRSD) scores. We also examined the "profile" measures of mean, maximum, and minimum of the three cortisol values; again, all three were significantly correlated with HRSD scores. To evaluate associations between clinical severity and HPA dysregulation at the pituitary level, we studied a second group of 44 patients with major depressive disorder. Each had postdexamethasone cortisol determinations at 4:00 PM and 11:00 PM as well as pre- and postdexamethasone beta-endorphin determinations at 4:00 PM. The cortisol data from this group followed the same pattern as in the first sample, and there was a significant relationship between HRSD score and degree of beta-endorphin nonsuppression as well. These results suggest that severity of depression is one of the determinants of dysregulation at both adrenal and pituitary levels of the HPA axis, accounting for 10%-20% of the observed variance.
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PMID:Postdexamethasone plasma cortisol and beta-endorphin levels in depression: relationship to severity of illness. 295 96

The factors controlling the expression of corticotropin-releasing hormone (CRH), a hypothalamic neuropeptide involved in the regulation of ACTH secretion, are poorly understood partly because a suitable in vitro model is lacking. To study the regulation of CRH gene expression, an 8-kilobase (kb) DNA fragment containing the entire human CRH gene as well as approximately 6 kb of 5' sequence and 0.8 kb of 3' sequence was isolated from a lambda Charon 4A human genomic library and introduced into a mouse anterior pituitary cell line, AtT-20, by CaPO4 transfection with a neomycin-selectable marker. Approximately 10% of the neomycin-resistant lines stably expressed the CRH gene and secreted radioimmunoassay-detectable CRH into culture media at levels greater than 100 pg/ml. By Southern blot analysis the 8-kb DNA fragment containing the CRH gene had been incorporated intact into the AtT-20 genome. In each CRH-producing strain, but not in the parent AtT-20 cell line, we detected by Northern blot analysis an RNA species that hybridized to two radioactive cRNA probes specific for either the 5' or 3' portion of CRH mRNA, and that co-migrated with placental CRH mRNA. Dexamethasone treatment for 24-96 h caused a specific decrease in CRH mRNA and peptide levels of 40-50% in the five CRH-producing cell lines with half-maximal suppression at approximately 10(-9) M dexamethasone, indicating that CRH gene expression is negatively regulated by glucocorticoids. Thus, we have established an in vitro model suitable for studying in detail those cis- and trans-acting factors which regulate CRH gene expression.
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PMID:Expression and dexamethasone regulation of the human corticotropin-releasing hormone gene in a mouse anterior pituitary cell line. 296 6

Synthetic ovine corticotropin-releasing factor (o-CRF) stimulated adrenocorticotropin (ACTH) release at the concentration of 10(-10) M or more in monolayer culture of rat anterior pituitary cells. Dexamethasone, 10(-7) M, inhibited this effect. In 5 healthy human subjects, o-CRF, 1 microgram/kg iv bolus, increased plasma ACTH levels from less than 10 pg/ml to 40.4 +/- 11.0 (mean +/- SD) after 30-60 min, and plasma cortisol from 12.8 +/- 2.8 micrograms/dl to 23.6 +/- 3.1 after 45-60 min. Of 7 patients with Cushing's disease (CD), five showed an exaggerated response of plasma ACTH and cortisol, one an exaggerated response of plasma ACTH but low response of plasma cortisol and the other no response of both hormones. The significant positive correlation between the inhibition of plasma cortisol by dexamethasone and the response of plasma ACTH and cortisol to o-CRF in CD was seen. No response of plasma ACTH and cortisol to o-CRF was seen in each one patient with Cushing's syndrome due to an adrenocortical adenoma, ectopic ACTH syndrome (but low response at retesting), isolated ACTH deficiency and Sheehan's syndrome. In one patient with Addison's disease an exaggerated response of plasma ACTH but no response of plasma cortisol was seen. In 4 of 5 healthy subjects and 5 of 7 patients with CD, plasma ACTH and cortisol levels showed a second peak at 120--210 min after o-CRF administration. To clarify the prolonged effect of o-CRF in human in vivo, the disappearance rates of injected o-CRF were evaluated by radioimmunoassay in 3 patients with cured Cushing's syndrome. A biexponential decay curve showed t1/2 values of 9.3 +/- 0.4 min and 79.6 +/- 0.7 min (mean +/- SE). From the chromatographic profile, a portion of injected o-CRF was thought to be bound to macromolecule (s). o-CRF, as a specific secretagogue of ACTH, is thought to be useful tool in evaluating patients with hypothalamo-pituitary-adrenal disorders.
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PMID:[Studies for clinical application of ovine corticotropin-releasing factor]. 298 91

Dexamethasone-suppressible hyperaldosteronism is a rare familial syndrome in which hypokalemia, suppression of plasma renin concentration, and elevated aldosterone secretion are corrected by treatment with glucocorticoids. Regulation of adrenocortical function and body electrolytes was studied in two affected brothers. Both were hypertensive (210/128 and 160/106 mm Hg) with hypokalemia (3.3 and 3.5 mM) and low plasma renin concentrations. Aldosterone was elevated intermittently with levels as high as 45 ng/dl (normal range, 4-16 ng/dl). Cortisol concentrations were normal but were correlated with aldosterone levels (r = 0.9 and 0.7). Concentrations of 11-deoxycorticosterone (19 and 21 ng/dl; normal range, 4-16 ng/dl) and 18-hydroxycortisol (1000 and 950 ng/dl; normal range, 34-150 ng/dl) were elevated, and diurnal changes in both were the same as those seen with aldosterone. Infusion of adrenocorticotropic hormone (ACTH) caused exaggerated increases of aldosterone, 11-deoxycorticosterone, and 18-hydroxycortisol; cortisol response was normal. A 4-week trial of dexamethasone normalized blood pressure and caused a natriuresis, a fall in aldosterone, and a rise in plasma renin. Administration of ACTH after dexamethasone treatment again caused exaggerated increases of aldosterone. Aldosterone did not respond to angiotensin II before dexamethasone therapy (r = 0.01), but it showed a normal response after therapy (r = 0.8, p less than 0.01). Neither administration of dopamine (1 microgram/kg/min) nor long-term therapy with bromocriptine (2.5 mg t.i.d. for 4 weeks) affected aldosterone biosynthesis. Thus, loss of dopaminergic inhibition of mineralocorticoid biosynthesis does not account for hyperaldosteronism in this condition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dexamethasone-suppressible hyperaldosteronism. Adrenal transition cell hyperplasia? 301 96

A radioimmunoassay (RIA) capable of determining blood ACTH levels in salmonid fishes was developed and validated. The RIA used an antibody raised against mammalian ACTH, iodinated human ACTH as tracer, and human 1-39 ACTH as standard. Incubation of the standard or unknown with antibody for 3 days before addition of as little high-specific activity tracer as practicable (1500 cpm; equivalent to 5 pg ACTH) produced a very sensitive RIA; the operating range was 5 to 200 pg ACTH/ml. Extracts of both pars distalis and neurointermediate lobe of the pituitary glands from a range of salmonid species diluted parallel to the ACTH standard in the RIA. There was always considerably more ACTH-immunoreactivity (ACTH-IR) in the pars distalis extracts than in the neurointermediate lobe. Generally plasmas also diluted parallel to the ACTH standard, with the exception only of the plasma from sexually mature female salmonids, which diluted very non-parallel to the standard, leading to unrealistically low estimates of the ACTH-IR level. The use of heparin as an anticoagulant during collection of samples caused problems when these plasmas were immunoassayed; instead EDTA was found to be a suitable anticoagulant. When the ACTH-IR was extracted from a pool of plasma obtained from acutely stressed salmon and chromatographed on a column of BioGel P6, followed by subsequent ACTH RIA of the fractions, only a single sharp peak of ACTH-IR was detected, which eluted in the position of authentic 1-39 ACTH. The plasma ACTH-IR level in unstressed fish was low, and near the detection limit of the RIA. An acute stress, produced by crowding and confinement for 30 min, increased ACTH-IR approximately 10-fold, and plasma cortisol levels 50-fold, but the plasma alpha-MSH level was not affected. Dexamethasone-treated fish did not respond to this stressor with any increase in either ACTH or cortisol levels.
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PMID:The development and validation of a radioimmunoassay to measure plasma ACTH levels in salmonid fishes. 302 60

In order to examine regulation of pituitary intermediate lobe secretion, plasma immunoreactive (i)ACTH, cortisol, and alpha-MSH responses to iv bolus injections of CRF, quipazine maleate (serotonin agonist), isoproterenol (beta-adrenergic agonist) or haloperidol (dopamine antagonist) were determined in conscious, unrestrained dogs. Endocrine responses to these test substances were also determined in dogs pre-treated with dexamethasone. Administration of one or more doses of each test substance resulted in significant elevations in plasma iACTH and cortisol concentrations. Only haloperidol injection caused significant increases in plasma i alpha-MSH. Following dexamethasone pre-treatment, plasma iACTH and cortisol increases in response to all test substances were considerably reduced or abolished. Dexamethasone did not alter baseline or haloperidol-stimulated plasma i alpha-MSH concentrations. However, infusion of bromocriptine mesylate (dopamine agonist) in combination with dexamethasone pre-treatment reduced the plasma i alpha-MSH response to haloperidol. We conclude that a dopaminergic pathway is important in the in vivo regulation of pituitary intermediate lobe activity in dogs.
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PMID:In vivo evidence for dopaminergic regulation of the canine pituitary intermediate lobe. 302 39


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