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)

Synthetic ovine corticotropin-releasing hormone (oCRH) is a potent and specific ACTH secretagogue in man. Threshold and maximal i.v. doses are 0.01-0.03 and 3-10 micrograms/kg or less, but increase in frequency, severity, and duration at higher doses. oCRH produces a biphasic plasma immunoreactive (IR)-ACTH response and has a prolonged duration of action that is probably due to its long circulating half-life. Other pro-opiomelanocortin IR-peptide are secreted concomitantly in equimolar amounts. Plasma IR-cortisol concentration tends to follow that of ACTH, but also reflects cortisol's longer circulating half-life and the fact that acutely the maximally-stimulating plasma IR-ACTH level is about 45 pg/ml. oCRH is as effective given s.c. as i.v., but intranasal administration is only 1% as effective. Sex and age have no effect on the plasma IR-ACTH and IR-cortisol responses to oCRH. The time of day of oCRH administration has little influence on the plasma IR-ACTH response, but the plasma IR-cortisol response is much greater to oCRH given later in the day than early in the morning. Plasma IR-ACTH response to oCRH is more dependent on the basal plasma IR-cortisol level than the time of day. Arginine vasopressin given at the same time as oCRH potentiates 4-fold the plasma IR-ACTH response to oCRH alone, almost to levels obtained with insulin-induced hypoglycemia. However, oCRH administered at the onset of insulin-induced hypoglycemia does not cause higher plasma IR-ACTH levels, indicating that endogenous CRH levels are maximally-stimulating during the hypoglycemic response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Corticotropin-releasing hormone: stimulation of ACTH secretion in normal man. 283 99

Human placenta contains the POMC-derived peptides ACTH, alpha MSH, and beta-endorphin, and CRH. High concentrations of immunoreactive (IR) CRH have been recently demonstrated in maternal plasma during pregnancy. To determine if the human placenta secretes CRH and POMC-derived peptides, we developed an in vitro human placental fragment perifusion system. The perifused tissue released IR-CRH and POMC-derived peptides at a constant rate for at least 5 h. The mean IR-CRH concentration in the effluent (under basal conditions) was 158 +/- 26 (+/- SD) pg (34.5 +/- 5.8 fmol)/5-min fraction.g tissue. IR-alpha MSH, IR-beta-endorphin, and IR-ACTH were also released into the perifusion medium; the mean concentration of alpha MSH released was 24.6 +/- 8 pg (14.8 +/- 4.8 fmol)/fraction.g, that of ACTH was 2.9 +/- 1.9 pg (0.65 +/- 0.43 fmol)/fraction.g, and that of beta-endorphin was 12.9 +/- 6 pg (3.8 +/- 1.7 fmol)/fraction.g. We examined the effects of human CRH, oxytocin, vasopressin, and dexamethasone on placental POMC peptide secretion. Five-minute pulses of 10(-8) or 10(-6) mol/L human CRH or oxytocin produced an immediate and dose-dependent increase in all POMC peptides in the effluent. A 5-min pulse of 10(-8) or 10(-6) mol/L vasopressin had no effect. A continuous 4-h exposure to 10(-6) mol/L dexamethasone had no effect on either basal IR-CRH or POMC-derived peptide or their KCl-induced release. In conclusion, we found that 1) human placenta releases IR-CRH and POMC-derived peptides in vitro; this phenomenon seems to be independent of glucocorticoid control; 2) placental CRH may have a paracrine effect on placental POMC peptide release in addition to its possible action on maternal pituitary hormone release; and 3) oxytocin, but not vasopressin, stimulates placental POMC peptide release.
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PMID:Corticotropin-releasing hormone and oxytocin stimulate the release of placental proopiomelanocortin peptides. 283 12

Plasma growth hormone (GH) release after injection of 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) was investigated in 11 patients with major depressive disorder and normal controls matched for gender, age, body weight and ovarian status. In contrast to controls, who exhibited no significant GH response to CRH, depressed patients showed a significant net increase in GH secretion following CRH administration. The abnormal GH response to CRH was not correlated with baseline corticotropin (ACTH) and cortisol nor with CRH-induced ACTH and cortisol response. The implications of these findings are discussed with reference to such factors as alpha-adrenergic hyperactivity, hypothalamic-pituitary system dysregulation, drug interference, non-specific stress responses and abnormal neuroendocrine circadian rhythms in major depression.
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PMID:Abnormal responsiveness of growth hormone to human corticotropin-releasing hormone in major depressive disorder. 283 39

Twenty-four subjects (12 patients with major depressive disorder and 12 controls matched for sex and age) received 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) as an iv bolus dose. Healthy subjects exhibited a slight, but sustained, increase of plasma delta sleep-inducing peptide (DSIP) concentrations, whereas a marked reduction of DSIP levels was found in depressives. Compared to controls, depressed patients showed a significant attenuation of corticotropin (ACTH) responses, whereas cortisol secretion in response to hCRH was normal. Basal DSIP and cortisol concentrations were highly correlated and were higher in depressives than in controls. Both were negatively correlated with the DSIP responses to hCRH. These findings are compatible with the hypothesis that hypothalamic-pituitary-adrenal (HPA) overactivity in the depressive state is primarily due to central hypersecretion of CRH and support the view of a modulatory function of DSIP in the complex regulatory mechanism of the HPA system and of its pathophysiological significance for aberrant HPA axis function in major depressive disorder.
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PMID:Delta sleep-inducing peptide response to human corticotropin-releasing hormone (CRH) in major depressive disorder. Comparison with CRH-induced corticotropin and cortisol secretion. 283 44

To explore the integrity of the hypothalamic-pituitary-adrenal (HPA) system in major depressive disorder, 12 patients and normal controls matched for sex, age, and body weight received 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) as an i.v. bolus dose. Compared to controls, depressed patients showed an elevation in baseline cortisol and a significant attenuation of net adrenocorticotropin (ACTH) responses, while cortisol secretion in response to hCRH was normal. These abnormalities in HPA axis function and apparent discordances in the interrelationships of ACTH and cortisol baseline and net stimulation responses between depressed patients and normal controls indicate, at least in part, a derangement of the glucocorticoid-dependent negative feedback circuitry and support the hypothesis that HPA hyperactivity in depression involves neurotransmitter-mediated hypothalamic hypersecretion of CRH.
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PMID:Corticotropin and cortisol response to human CRH as a probe for HPA system integrity in major depressive disorder. 283 59

The acute and chronic effects of secretagogues activating cAMP-dependent pathways (CRH and cAMP) and activating cAMP-independent pathways [phenylephrine and phorbol 12-myristate 13-acetate (PMA)] on anterior pituitary function were examined in serum-free cultures. Applied acutely, PMA produced a greater stimulation of ACTH/endorphin secretion than CRH or cAMP. However, the effects of CRH and cAMP on secretion were maintained for up to 12 days, while those of PMA and phenylephrine diminished rapidly. Secretagogue effects on pro-ACTH/endorphin biosynthesis were determined by immunoprecipitation of biosynthetically labeled beta-endorphin-related peptides. Cultures exposed to CRH or cAMP and [3H]tyrosine for 12 h produced 1.7 +/- 0.2- and 1.6 +/- 0.1-fold more newly synthesized beta-endorphin-related material than control cells. Cultures exposed to phenylephrine or PMA synthesized 1.3 +/- 0.1- and 1.4 +/- 0.1-fold more peptide than control cells. Exposure of cells to CRH or cAMP for 12 days increased pro-ACTH/endorphin biosynthesis to a greater extent than the 12-h treatment (3.0 +/- 0.1- and 2.5 +/- 0.3-fold over control value, respectively). Exposure to phenylephrine or PMA for 12 days had the same effect on pro-ACTH/endorphin biosynthesis as exposure for 12 h. After acute or chronic secretagogue exposure, the cells secreted relatively more newly synthesized beta-lipotropin than beta-endorphin. Levels of pro-ACTH/endorphin mRNA in cultures treated acutely (12 h) or chronically (12 days) with CRH, cAMP, or phenylephrine changed in parallel with rates of pro-ACTH/endorphin biosynthesis. In contrast, chronic exposure to PMA stimulated biosynthesis while reducing pro-ACTH/endorphin mRNA levels. In summary, these results suggest that factors that activate cAMP-dependent pathways are more powerful stimulators of pro-ACTH/endorphin biosynthesis than factors that activate cAMP-independent pathways; the cAMP-dependent pathway may be primarily responsible for regenerating depleted hormone reserves.
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PMID:Comparison of acute and chronic secretagogue regulation of proadrenocorticotropin/endorphin synthesis, secretion, and messenger ribonucleic acid production in primary cultures of rat anterior pituitary. 284 Feb 62

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

Earlier observations in our laboratory indicated that i.v. infusion of human/rat corticotropin-releasing hormone (hCRH) suppresses pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in ovariectomized rhesus monkeys. Since cortisol secretion increased significantly as well, it was not possible to exclude the possibility that this inhibitory effect of hCRH on gonadotropins was related to the activation of the pituitary/adrenal axis. The purpose of the present study was to determine the role of pituitary/adrenal activation in the effect of hCRH on LH and FSH secretion. We compared the effects of 5-h i.v. infusions of hCRH (100 micrograms/h, n = 7) and of human adrenocorticotropic hormone (ACTH) (1-24) (5 micrograms/h, n = 3; 10 micrograms/h, n = 3, 20 micrograms/h, n = 3) to ovariectomized monkeys on LH, FSH, and cortisol secretion. As expected, during the 5-h ACTH infusions, cortisol levels increased by 176-215% of baseline control, an increase similar to that observed after CRH infusion (184%). However, in contrast to the inhibitory effect observed during the CRH infusion, LH and FSH continued to be released in a pulsatile fashion during the ACTH infusions, and no decreases in gonadotropin secretion were observed. The results indicated that increases in ACTH and cortisol did not affect LH and FSH secretion and allowed us to conclude that the rapid inhibitory effect of CRH on LH and FSH pulsatile release was not mediated by activation of the pituitary/adrenal axis.
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PMID:The inhibitory action of corticotropin-releasing hormone on gonadotropin secretion in the ovariectomized rhesus monkey is not mediated by adrenocorticotropic hormone. 284 Sep 81

In order to evaluate the secretion of beta-endorphin in obese children and adolescents, we measured plasma beta-endorphin, ACTH and cortisol levels before and following administration of CRH (1 microgram/kg). Fourteen normal weight and 22 obese subjects (weight excess ranging from 30 to 98%) were studied. Plasma hormone levels were measured by radioimmunoassay directly in plasma (cortisol, ACTH) and after silicic acid extraction and Sephadex G-75 column chromatography (beta-endorphin). Basal beta-endorphin levels in obese children were significantly higher than in controls (14.7 +/- 1.8 vs 6.0 +/- 0.6 pmol/l; mean +/- SEM). No differences were found in basal ACTH and cortisol levels. CRH administration significantly increased beta-endorphin, ACTH and cortisol levels in normal subjects and ACTH and cortisol levels in obese subjects. Plasma beta-endorphin levels in obese children and adolescents did not show any significant increment. These data confirm the higher than normal beta-endorphin plasma levels in obese subjects in childhood and demonstrate that CRH is unable to increase beta-endorphin levels, suggesting an impairment of the hypothalamo-pituitary control mechanisms or an extra-anterior pituitary source.
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PMID:Impaired beta-endorphin response to human corticotropin-releasing hormone in obese children. 284 94

Ovine corticotropin-releasing hormone (1 micrograms/kg body weight) and arginine vasopressin (1 micrograms/kg) were injected iv in sheep, both separately and in combination. Plasma were sampled just before and 5, 15 and 30 min after the injection. Adrenocorticotropin-related peptides were isolated by Sephadex G-50 column chromatography and measured by RIA. Cortisol and aldosterone were determined on the same plasma samples. Three molecular forms of immunoreactive ACTH (IR-ACTH) were isolated: 'big' (greater than 20,000 mol wt), 'intermediate' (= 8000 mol wt) and 'little' (= 4500 mol wt). Following CRH injections, the three molecular forms of ACTH were enhanced, particularly the 'little' form, whereas 'intermediate' IR-ACTH was highly and specifically responsive to AVP. After a simultaneous injection of CRH and AVP, additive increases occurred for 'intermediate' and 'little' IR-ACTH. The release of different molecular forms of IR-ACTH after stimulation by CRH or AVP of corticotrope cells suggests that ACTH-related peptides could be stored in different intracellular pools or secreted by different pituitary cells.
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PMID:Plasma concentrations of adrenocorticotropin-related peptides after corticotropin-releasing hormone and vasopressin injections in sheep. 284 71


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