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)

To explore the interrelationships between the serotoninergic system and the hypothalamic-pituitary-adrenal (HPA) axis in human obesity, we evaluated cortisol and adrenocorticotropic hormone (ACTH) response to synthetic human corticotropin-releasing hormone (hCRH, 1 microgram/kg intravenously [IV]) before and after stimulation of the serotoninergic system by dextrofenfluramine (d-FF, 30 mg/d for 3 months) in nine obese women. These responses were compared with a CRH test (1 microgram/kg) carried out in nine age-matched normal-weight women. Plasma cortisol of obese subjects did not significantly increase after CRH (peak value 127.1 +/- 11.2 ng/mL v 104.1 +/- 9.5 ng/mL). This response was lower (P less than .005) than in the controls, in whom the basal cortisol value of 120.6 +/- 11.8 ng/mL reached a peak value of 221.2 +/- 13.4 ng/mL. However, after administration of d-FF, CRH significantly increased (P less than .0001) plasma cortisol (peak value 170.6 +/- 18.0 ng/mL v 111.5 +/- 10.8 ng/mL) and the response was enhanced (P less than .05) as compared with that obtained before d-FF. The ACTH levels of our patients showed a small increment after CRH injection (peak value 13.5 +/- 1.7 pg/mL v 9.6 +/- 1.1 pg/mL), but the hormonal response was lower (P less than .005) than in controls (peak value 38.1 +/- 5.5 pg/mL v 13.8 +/- 0.8 pg/mL). However, after d-FF, CRH induced a significant increment (P less than .05) in plasma ACTH at 30 minutes (20.4 +/- 3.7 pg/mL v 10.9 +/- 0.9 pg/mL) and 45 minutes (18.0 +/- 2.6 pg/mL), even though this response was not significantly different from that observed before d-FF administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotoninergic receptor activation by dextrofenfluramine enhances the blunted pituitary-adrenal responsiveness to corticotropin-releasing hormone in obese subjects. 131 2

1. The possible correlation between secretions of adrenocorticotropic hormone (ACTH) and of beta-lipotropin (beta-LPH), two pro-opiomelanocortin (POMC)-derived peptides, was investigated in 27 normal subjects under basal conditions (circadian rhythm), after the administration of 1 mg dexamethasone and in tests involving acute (human corticotropin releasing hormone, hCRH, and insulin tolerance test, ITT) and chronic (metyrapone) stimulation. 2. All subjects presented circadian rhythm and an operating negative feedback mechanism. Plasma ACTH and beta-LPH concentrations were correlated in all tests. The increase in ACTH and beta-LPH levels after hCRH was lower than that detected after ITT, though both increases were more discrete than those detected after stimulation with metyrapone. 3. The data suggest that, under hypoglycemic conditions, ACTH and beta-LPH secretion involves other POMC secretagogues in addition to endogenous CRH. The nature of these factors remains undefined. The greater efficacy of metyrapone treatment in elevating ACTH and beta-LPH levels is most likely mediated by sustained reduction in cortisol production and interruption of the rapid steroid feedback on the pituitary. 4. The molar peak ratios of the acute tests, which were similar to one another, differed from the peak ratio obtained during the metyrapone test, suggesting that corticotrophs may present pools with differentiated ACTH and beta-LPH content and release according to the type and/or duration of the stimulus.
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PMID:Beta-lipotropin/adrenocorticotropic hormone responses to corticotropin releasing hormone, hypoglycemia, metyrapone and dexamethasone in normal human subjects. 196 79

Synthetic human and ovine corticotropin-releasing hormone (hCRH, oCRH) are commonly used as a diagnostic tool of the hypothalamo-pituitary-adrenal axis. In this paper reports about side effects after various modes of CRH-application are analyzed and compared to our corresponding data of human studies with hCRH and oCRH. Generally, CRH is well tolerated after single administration and interval-application of standard doses, although minor side effects appear sometimes after higher doses (greater than 200 micrograms hCRH, oCRH) of CRH-bolus-injections. Predominantly the cardiovascular system (e.g. tachycardia, hypotension, flushing) is affected; neuropsychological symptoms are only seen sporadically (e.g. dizziness). Long term continuous infusion (several hours) of low CRH-doses (hCRH, oCRH) are well tolerated but side effects appear (see above) when cumulated doses of 200 micrograms-300 micrograms/h are given. Standard doses of hCRH and oCRH are also well tolerated in severely ill patients; it has to be considered that higher doses may provoke marked side effects in persons with neurologic disorders, in subjects with coronary heart disease and in patients with endocrinological disorders of the pituitary-adrenal axis, especially in those subjects in whom the blood-brain-barrier may have been damaged (e.g. head injury, intracranial operation). Single hCRH- and oCRH-bolus-injections in standard doses have a very low rate of complications, "non-standard" doses should provisionally be used only in clinical studies with well designed safety-precautions.
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PMID:Safety and side effects of human and ovine corticotropin-releasing hormone administration in man. 203 13

Specific in vivo neutralization was used in an attempt to explore the roles of corticotropin-releasing hormone (CRH), ACTH, and beta-endorphin during surgical stress in Sprague-Dawley rats. Rats were randomly assigned to groups (n = 20-30/group) that received iv injections of rabbit antirat/human CRH (anti-r/hCRH), antihuman ACTH (anti-hACTH), antihuman beta-endorphin (anti-h beta-endorphin), or normal rabbit serum. Three hours later all animals were subjected to a uniform stress consisting of ether anesthesia, surgical laparotomy, and phlebotomy of 7 ml via the inferior vena cava. Survival rates were recorded, and RIAs were performed for ACTH, beta-endorphin, and corticosterone. Rats treated with anti-h beta-endorphin had a survival rate of 64%, which was significantly higher than that of the control group (33%; P less than 0.025, by analysis of variance). Anti-r/hCRH or anti-hACTH treatment was not associated with a change in survival rate. Plasma immunoreactive beta-endorphin levels were markedly decreased in the group treated with anti-h beta-endorphin (P less than 0.0001). Anti-r/hCRH had no effect on plasma immunoreactive ACTH or beta-endorphin. Plasma immunoreactive ACTH and corticosterone levels were decreased in the group treated with anti-hACTH (P less than 0.0001 and P less than 0.01, respectively). We conclude that 1) beta-endorphin immune neutralization is associated with a survival advantage during severe surgical stress, suggesting that circulating beta-endorphin might have deleterious effects during stress; 2) In severe stress, acute immune neutralization of CRH is not sufficient to inhibit ACTH, beta-endorphin, and corticosterone secretion, suggesting significant involvement of other secretagogues of the pituitary-adrenal axis; and 3) moderate decreases in corticosterone cannot affect survival, presumably because glucocorticoids play only a permissive role in maintaining cardiovascular stability during surgical stress.
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PMID:Effects of immune neutralization of corticotropin-releasing hormone, adrenocorticotropin, and beta-endorphin in the surgically stressed rat. 282 12

There is evidence that the peptides derived from proopiomelanocortin as well as the neurohypophyseal hormones exert important and substantial effects on brain functions after intracerebroventricular and peripheral administration. This led us to study the effects of intravenous hCRH on brain functions in humans using electroencephalographic techniques. In our experience the event-related potentials (e.g. auditory evoked potentials) provide a sensitive and accurate assay systems to study such effects of peptides. Male volunteers were tested in a dichotic listening paradigm, providing electrophysiological measures of selective attention. Human CRH (50 micrograms/hr i.v.) augmented selective attention as indicated by an increased difference between evoked potential waveforms to attended and to unattended stimuli. The opposite results, a decrease in selective attention, was observed after treatment with the behavioral active fragment of adrenocorticotropin, ACTH 4-10. In comparison to ACTH 4-10, lysine-vasopressin, and cortisol, CRH displayed a unique pattern of influences on event related potentials. From these results we conclude that CRH can affect brain function in man and does so by a direct action on the brain and not only by stimulating the release of other behavioral active hormones.
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PMID:Effects of corticotropin releasing hormone on human brain function: an analysis based on auditory evoked potentials. 283 98

Atrial natriuretic hormone (ANH) is found in heart myocytes, and also in the CNS. The inhibitory action of ANH on the hypothalamic-pituitary-adrenocortical (HPA) system has been established by in vivo and in vitro experiments, and could be of considerable importance: whereas several synergists to corticotropin-releasing hormone (CRH), the key hormone of the HPA system, are characterized in the past, until now ANH seems to be the only peptide which counterbalances the effects of CRH at the pituitary. As well as at the corticotroph, CRH has a stimulatory influence upon the lactotroph in vivo, and like ACTH and corticosteroids prolactin (PRL) is released in response to physical and cognitive challenges. To test the hypothesis of whether ANH also inhibits the CRH-mediated prolactin release a randomized, placebo-controlled, double-blind study in 12 males aged from 25 to 30 years was conducted. With regard to the diurnal variation of the HPA system activity we compared the prolactin release by 100 micrograms hCRH during a 30 min infusion of placebo, 150 micrograms ANH or 3 IU arginine vasopressin in the morning (08:00 h) and evening (19:00 h). Evaluation of morning and evening effects revealed that administration of hCRH led to a prompt rise of plasma PRL concentration. Infusion of ANH resulted in a significantly reduced maximum increment of PRL compared to placebo (0.83 +/- 0.87 vs 2.85 +/- 1.57 ng/ml, mean +/- SD, n = 12, p < .001). In addition, the AUC values were significantly lower under ANH than in the placebo condition. Infusion of AVP did not significantly change the PRL response to CRH vs placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atrial natriuretic hormone inhibits corticotropin-releasing hormone-induced prolactin release in man. 762 56

In order to investigate whether modulation of the effects of corticotropin-releasing hormone (CRH) by arginine vasopressin (AVP) and atrial natriuretic hormone (ANH) is sensitive to circadian fluctuations, 12 healthy male volunteers were administered 100 micrograms hCRH during 30 min infusion of placebo, 3 IU AVP, or 150 micrograms ANH, the experiment being carried out in the morning (0800h) or in the evening (1900h). Compared with placebo, AVP significantly amplified the CRH-induced adrenocorticotropin hormone (ACTH) surge both in the morning and in the evening, whereas it enhanced cortisol secretion only in the evening. In contrast, ANH significantly reduced the ACTH surge, but only in the evening, and it reduced the cortisol surge in the morning compared to the evening. During ANH infusion plasma AVP levels were suppressed both in the morning and in the evening, pointing to a hypothalamic site of action in addition to the pituitary and adrenocortical effects. The ACTH secretion profiles were indistinguishable between morning and evening in all three experimental conditions, whereas cortisol profiles differed significantly depending on the time of day in the AVP and ANH condition, but not for placebo.
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PMID:Circadian changes in the sensitivity of the corticotropin-releasing hormone-stimulated HPA system after arginine vasopressin and atrial natriuretic hormone in human male controls. 767 36

This study compared plasma concentrations of adrenocorticotropin (ACTH) and cortisol in young men (N = 10, mean age 24.4 years), young women (N = 10, mean age 25.4 years), old men (N = 8, mean age 81.6 years) and old women (N = 8, mean age 83.5 years) under basal resting conditions and after stimulation with either human corticotropin-releasing hormone (hCRH, 100 micrograms iv) or a combined injection of hCRH (100 micrograms) and arginine vasopressin (VP, 0.5 IU iv). Basal secretion of cortisol did not differ among groups, but basal concentrations of ACTH were diminished in young women (p < 0.01), indicating an enhanced adrenal sensitivity to ACTH in these subjects. Pituitary responses to hCRH did not differ between young men and women. However, responses to hCRH/VP were stronger in the young females (p < 0.01), suggesting an enhanced pituitary responsiveness to the augmenting effect of VP on ACTH release in this group. Pituitary-adrenal secretory responses were greater in old than in young men after sole injection of hCRH (p < 0.05) and even more so after combined injection of hCRH/VP (p < 0.01). In old women, pituitary-adrenal secretory responses were also greater than in young women (p < 0.05). But, in particular for responses to hCRH/VP, these effects were less distinct than within the men. Results indicate an enhancing effect of age on pituitary responsiveness to the hypothalamic secretagogues hCRH and VP, modulated by the subject's gender.
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PMID:Effects of age and gender on pituitary-adrenocortical responsiveness in humans. 778 10

The vasoactive effects of corticotropin-releasing hormone (CRH) in the human fetal-placental circulation in vitro have been investigated. Single lobules of term placentae were bilaterally perfused with constant flows of Krebs' solution (maternal and fetal, 5 ml/min, 95% O2, 5% CO2, 37 degrees C, pH 7.3) and changes in fetal-placental arterial perfusion pressure measured. Effects of human (hCRH) and ovine (oCRH) CRH were examined during submaximal vasoconstriction (100-120 mmHg) of the fetal-placental vasculature induced by prostaglandin F2 alpha (PGF2 alpha), (0.7-2 mumol/L). During infusion of hCRH or oCRH (24-7000 pmol/L) a concentration-dependent vasodilatation was observed. Human CRH and oCRH were equipotent as vasodilator agents (regression analysis; P > 0.05; n = 5). The vasodilator response curves to human and ovine CRH were compared to prostacyclin (PGI2) (1.2-1180 nmol/L). Human and oCRH were 53 times more potent than PGI2 (regression analysis, P < 0.05; n = 5). These results indicate that CRH has powerful vasodilator properties in the human fetal-placental circulation and may play a role in control of placental vascular resistance to blood flow.
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PMID:Corticotropin-releasing hormone-induced vasodilatation in the human fetal placental circulation. 804 90

General pharmacological effects of the human corticotropin-releasing hormone, corticorelin (human) (CAS 86784-80-7), on the central nervous system, somatic nervous system, autonomic nervous system and smooth muscle, respiratory and circulatory system, digestive system and miscellaneous organs were investigated. 1. The central nervous system: Corticorelin (human) had little effect on hexobarbital-induced sleeping-time, maximal electroshock-induced convulsion, acetic acid-induced writhing, rota-rod performance. Corticorelin (human) at doses of more than 10 micrograms/kg i.v. induced flush of skin and pilo-erection, at doses of more than 30 micrograms/kg i.v. decreased body temperature, delayed expression of perphenazine-induced catalepsy and indicated hunched posture, and at the dose of 100 micrograms/kg i.v. induced the rise of awake-level and decrease of the total power of EEG, and decreased the spontaneous motor activity. 2. The somatic nervous system: Corticorelin (human) did not cause muscle relaxation in mice and had little effect on neuromuscular transmission in rats. No local anesthetic activity of corticorelin (human) was exhibited through inhibition of the corneal reflex in guinea pigs. 3. The autonomic nervous system and smooth muscle: Corticorelin (human) had no effect on the contraction of isolated ileum of guinea pigs induced by histamine and acetylcholine, and on the contraction of isolated trachea of guinea pigs induced by histamine, and the pupil diameter of rabbits. Corticorelin (human) at doses more than 30 micrograms/kg i.v. decreased spontaneous motility and contractile force of uterus of non-pregnant rabbits. 4. The respiratory and circulatory system: Corticorelin (human) had no effect on the contraction of isolated aorta of rats induced by norepinephrine. Corticorelin (human) at doses of more than 3 micrograms/kg i.v. decreased the blood pressure, increased heart rates and slightly increased the number of respiration in dogs. However, corticorelin (human) had no effect on ECG and femoral blood flow in dogs. 5. The digestive system: Corticorelin (human) at doses of more than 0.3 microgram/kg i.v. increased duodenal motility and contractile force, at doses of more than 1 microgram/kg i.v. increased colonic contractile force transiently and increased antral motility. Corticorelin (human) at doses of more than 3 micrograms/kg i.v. caused diarrhea and at doses of more than 30 micrograms/kg i.v. inhibited small intestinal propulsion in mice. Corticorelin (human) at dose of 100 micrograms/kg i.v. showed an inhibition of the gastric juice secretion and decreased the excretion of Na+, Cl- and H+ in rats. Corticorelin (human) produced slight gastric damages only at the highest dose of 100 micrograms/kg i.v.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:General pharmacological properties of the human corticotropin-releasing hormone corticorelin (human). 805 70


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