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)

Acute unilateral nephrectomy (AUN) causes natriuresis from the contralateral kidney through neurohumoral reflex pathways that involve an increase in the plasma of peptides derived from the N-terminal region of the adrenocorticotropic hormone (ACTH)/beta-endorphin precursor proopiomelanocortin (POMC). To determine the specificity of these humoral changes, the concentrations in plasma of ACTH and two peptides arising from the N-terminal fragment (NTF) of POMC, NTF32-49 and gamma-melanocyte-stimulating hormone (gamma-MSH), and of another natriuretic peptide, atrial natriuretic peptide (ANP), were measured by RIA with highly specific antisera to these epitopes. Group I experiments followed the course of sodium excretion (UNaV) for 120 min after AUN or sham nephrectomy. UNaV more than doubled within 60 min of AUN, and this natriuresis was maintained for the remainder of the experiment, whereas UNaV in sham rats did not change. There was no difference in plasma immunoreactive (ir) ACTH or ir-ANP concentrations between sham and AUN rats 120 min after the procedure, but plasma ir-NTF concentration was double in AUN rats compared with sham (P < 0.03). In Group II experiments, animals were killed 30, 60, 90, or 120 min after AUN and the urinary response related to peptide concentrations in plasma. UNaV rose rapidly after AUN, reaching a maximum value within 45 min that again was double the control value and remained stable for the duration of the experiment, up to 120 min after AUN. There was no significant change in ir-ACTH or ir-ANP at any point after AUN compared with values in sham AUN rats. However, plasma concentrations of both ir-NTF and ir-gamma-MSH were elevated 30 min after AUN and reached values at 120 min that were again double the values in sham rats (P < 0.05 for both).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute unilateral nephrectomy elicits a specific increase in plasma of peptides derived from the N-terminal region of proopiomelanocortin. 133 5

A possible catecholaminergic regulation of hypothalamic alpha-melanocyte-stimulating hormone (alpha-MSH) has been investigated in male rats by an in vivo approach. The hormone was measured by radioimmunoassay in three hypothalamic regions: medial basal hypothalamus, preoptic hypothalamic area and dorsolateral hypothalamus. The tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (300mg/kg) increased the hypothalamic alpha-MSH content in medial basal hypothalamus and preoptic hypothalamic area when it was measured at 22:00 h. Diethyldithiocarbamate (600mg/kg), which inhibits dopamine beta-hydroxylase, as well as 2-3-dichloromethylbenzylamide (25mg/kg), which acts on the phenylethanolamine-NCH3 transferase also increased the alpha-MSH content in the above mentioned discrete areas. The alpha-adrenoceptor antagonist phenoxybenzamine (15mg/kg), as well as the alpha 1-adrenoceptor antagonist prazosin (1.0mg/kg), also increased the hypothalamic alpha-MSH content in medial basal hypothalamus and preoptic hypothalamic area. None of these agents modified alpha-MSH content in dorsolateral hypothalamus. Haloperidol (1.2mg/kg), a dopaminergic receptor antagonist, propranolol (6.0mg/kg) and yohimbine (10mg/kg) (non selective beta- and alpha 2-adrenergic antagonist drugs respectively) had no effect on the alpha-MSH in any of the hypothalamic areas studied. These results indicate that the catecholaminergic system is involved in the control of proopiomelanocortin derived hypothalamic alpha-MSH through an alpha 1-adrenoreceptor. The data suggest that the control mechanism in the two alpha-MSH hypothalamic pools are different.
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PMID:Evidence for catecholaminergic control of alpha-melanotropin (alpha-MSH) content in hypothalamic areas. 136 45

In the ewe, estradiol and progesterone inhibit luteinizing hormone (LH) secretion during the breeding season. Endogenous opioid peptides (EOP) are also inhibitory to LH secretion, and both estrogen and progesterone have been reported to enhance EOP inhibition of LH release. Which EOP are involved in this inhibition is unclear. In this study, we concentrated on beta-endorphin because evidence for its ability to inhibit LH secretion exists in ewes. We first studied the distribution of beta-endorphin-immunoreactive neurons in 4 cycling ewes using immunocytochemistry. Cell bodies were found only within the medial basal hypothalamus (MBH) and were concentrated in arcuate nucleus and mammillary recess of the third ventricle, with a few in the median eminence. Extensive fiber tracts were seen in preoptic area (POA) and median eminence. We next tested the hypothesis that gonadal steroids increase the synthesis of EOP by measuring levels of mRNA for proopiomelanocortin (POMC), the precursor to beta-endorphin. Ovariectomized ewes were treated with no steroids (n = 7) or given subcutaneous Silastic implants containing either estradiol (n = 6) or progesterone (n = 6). After 4 days of treatment, EOP inhibition of LH secretion was measured by determining the LH response to WIN 44,441-3 (WIN), an EOP antagonist. LH pulse frequency and pulse amplitude were determined in blood samples collected at 12-min intervals for 3 h before and after intravenous administration of 12.5 mg WIN. WIN injection increased (p < 0.01) the LH pulse-frequency only in progesterone-treated and pulse amplitude only in estradiol-treated ewes. After blood sampling, the ewes were killed, and POA, MBH, and pituitary gland were removed. Total RNA was extracted from these tissues and dot blotted onto nitrocellulose membranes for hybridization with a DNA probe complementary to the POMC mRNA. The resulting autoradiographs were quantified densitometrically. Levels of POMC mRNA in the MBH were increased (p < 0.01) by both estradiol and progesterone as compared with the no steroid group. There was no detectable POMC mRNA in the POA. These results suggest that estrogen and progesterone enhance EOP inhibition of LH secretion by increasing POMC mRNA levels and thus synthesis of beta-endorphin.
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PMID:Immunocytochemical localization of beta endorphin and gonadal steroid regulation of proopiomelanocortin messenger ribonucleic acid in the ewe. 136 89

Ras proteins are enriched in neurosecretory cells suggesting that ras may play an important role in regulating the differentiated properties of such cells. We introduced the human H-ras oncogene, EJ-ras, into the model secretory cell line AtT20 to determine the effects of ras oncogene expression on neuropeptide synthesis and release. We report here that both of these processes are changed in ras-transfected AtT20 cells. Stimulated release of the pituitary hormone corticotropin is reduced, and transcription of the gene encoding its precursor, proopiomelanocortin, is down-regulated. At the same time, expression of other genes, both housekeeping and neural-specific, remain relatively unchanged. The alteration of proopiomelanocortin expression in AtT20 cells following ras oncogene transformation supports the hypothesis that ras may play a role in the determination of the differentiated phenotype of neurosecretory cells.
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PMID:Expression of the c-Harvey ras oncogene alters peptide synthesis in the neurosecretory cell line AtT20. 137 31

The human placenta has been implicated as a source of numerous peptide hormones during pregnancy. Since the immunoassay detection of the proopiomelanocortin derived peptide beta-endorphin (beta E) in placental extracts in 1978, it has remained uncertain whether placental beta E immunoreactivity (IR) is 1) secreted into the maternal circulation and 2) opiate receptor active during pregnancy. To elucidate the nature of beta E IR in the placenta, both beta E IR and N-alpha-acetylated beta E (Ac beta E) IR were simultaneously measured in extracts of human pituitaries, placentas, and plasma by two homologous RIAs. Pituitary extracts (n = 6) contained 38 +/- 7 nmol beta E IR per g wet wt tissue (mean +/- SEM), of which only 20 +/- 4 pmol/g were Ac beta E IR. Term placental extracts (n = 19) had 201 +/- 30 fmol/g wet wt total beta E IR and 30 +/- 3 fmol/g wet wt total Ac beta E IR, which comprised 15% of total beta E IR in placental extracts. Total plasma beta E IR rose from 28 weeks gestation (8.5 +/- 0.3 fmol/mL, n = 159) to peak at labor (50 +/- 4 fmol/mL, n = 98; P < 0.01) but total Ac beta E IR was found in only four 28-week (1.7 +/- 0.9 fmol/mL) and 42 labor plasma samples (0.9 +/- 0.1 fmol/mL). Gel filtration chromatography of placental and pituitary extracts showed that while less than 1% of the beta E31-size material was acetylated in the pituitary, up to 60% of the beta E31-size material in placental extracts was acetylated. In pooled third trimester plasma extracts, however, only 4% of the beta E31-size material was acetylated. Furthermore, the ratio of beta E31:beta-lipotropin in pituitary extracts (n = 3) was 0.5; pooled plasma-0.5, and placental extracts (n = 5)-1.2. These data indicate that 1) the placenta extensively N-alpha-acetylates beta E31 destroying its opiate bioactivity while the pituitary does not; 2) beta E IR in pregnant women's plasma is similar to pituitary beta E IR, being mostly nonacetylated and similar in size to beta-lipotropin. These findings are consistent with a pituitary source for the elevated plasma beta E IR found during late pregnancy which may, in turn, be a consequence of elevated plasma concentrations of placentally secreted plasma corticotropin-releasing factor IR present during the third trimester.
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PMID:Beta-endrophin immunoreactivity during human pregnancy. 146 47

It is thought that certain actions of ethanol involve an interaction with endogenous opioids, including proopiomelanocortin-derived peptides such as beta-endorphin. To examine this possibility, we used a sensitive and specific assay for proopiomelanocortin mRNA to obtain an estimate of the activity of the endorphinergic system in the mediobasal hypothalamus and the pituitary of rats exposed for 10 days in an inhalation chamber to either ethanol or water. This protocol causes dependence in the ethanol-exposed group, as demonstrated by the presence of withdrawal seizures after cessation of treatment. While ethanol treatment did not affect proopiomelanocortin mRNA levels in the pituitary, the level in hypothalamus was significantly lower in the ethanol-treated animals than in controls. These results suggest that some effect of ethanol may involve the hypothalamic endorphinergic system.
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PMID:Proopiomelanocortin messenger RNA is decreased in the mediobasal hypothalamus of rats made dependent on ethanol. 147 70

Adrenocortical function studies were performed in seven Dandie Dinmont terriers with pituitary-dependent hyperadrenocorticism. The ability of dexamethasone at a dose rate of 0.1 mg/kg body weight to suppress cortisol secretion was only moderate in four out of the six dogs tested. Concentrations of alpha-melanocyte-stimulating hormone in plasma were highly increased. Responses to stimulation with corticotrophin-releasing hormone and the dopamine-antagonist haloperidol, examined in three animals, were moderate or absent. These results indicate that adrenocortical stimulation, i.e. hyperadrenocorticotrophism, was caused by pituitary lesions which were functioning autonomously. In six of the seven animals there was a very close familial relationship and the coefficients of relationship and the coefficients of inbreeding were significantly higher than in a representative control population. It was concluded that these seven related terriers with hyperadrenocorticotrophism had the biochemical characteristics of de-novo neoplasms of proopiomelanocortin-producing cells, and there was evidence for a genetic involvement in tumorigenesis.
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PMID:Pituitary-dependent hyperadrenocorticism in a family of Dandie Dinmont terriers. 148 6

beta-Endorphin, an opioid peptide that contains 31-amino acids derived from proopiomelanocortin, has been implicated in a variety of disorders. To understand its role in pathophysiological states, its levels have been determined in body fluids, particularly in serum or plasma, with the use of commercially available radiometric assay kits. Because the circulating levels of this endogenous opioid peptide are small and antibodies can cross-react with chemically related peptides to different degrees and give rise to faulty interpretation of the data, the performance characteristics of the available radioimmunoassay kits for beta-endorphin from the Immuno Nuclear Corporation, Stillwater, Minn, the New England Nuclear Corporation, Boston, Mass, and the Nichols Institute, San Juan Capistrano, Calif, were evaluated. In overall performance, the Nichols kit was found to be the most reliable in this laboratory, even though the sensitivity of the Immuno Nuclear kit was better at lower concentrations of beta-endorphin. Serum was better than plasma in terms of recovery of beta-endorphin. When collected on ice, no significant loss in beta-endorphin immunoreactivity was observed at 1 hour. The use of edetic acid (EDTA), siliconized edetic acid, and aprotinin (Trasylol)-added siliconized edetic acid tubes was not helpful in improving the performance of the assay. The optimal condition to collect the specimen was to use glass tubes, place the glass tubes on ice immediately, separate the serum, and freeze the sample within 1 hour of collection.
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PMID:Detection of beta-endorphin in human blood. A study of performance characteristics of different radiometric systems. 149 63

In mammals, proopiomelanocortin-related peptides are involved in reproductive processes both at the hypothalamo-pituitary and ovarian levels. Using immunocytochemical, biochemical and physiological "in vitro" studies, we provide here evidence for a diffuse POMC-related opioid system in the frog Rana esculenta. Ovarian beta-endorphin (beta-EP) is expressed in thecal cells and changes during the reproductive cycle in an inverse relationship with follicular development. Seasonal changes in the ovary are different to those in the brain or in the pituitary. The ratio of acetylated vs native beta-EP in the ovary also changes over the reproductive period, affecting the biological activity of the peptide. During both the reproductive spring period and the summer post-reproductive phase pMol amounts of beta-EP stimulate follicular androgen secretion in vitro, in a naloxone-reversible way. In either period, an inhibition of estradiol, possibly mediated via other factors, is the result of opioid action. In conclusion, these data demonstrate for the first time the widespread presence of beta-EP-related peptides in the frog Rana esculenta. Both immunocytochemical and biochemical evidence, as well as in vitro responses, support a physiological role for beta-EP in ovarian seasonality during the reproductive cycle of this amphibian.
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PMID:Ovarian opioids and the reproductive cycle of the frog Rana esculenta. 157 72

In the intermediate lobe of the pituitary gland, the prohormone proopiomelanocortin (POMC) is processed to, among other peptides, melanocyte-stimulating hormone (alpha-MSH). In the toad Xenopus laevis alpha-MSH controls skin darkening during background adaptation, and the level of POMC gene transcription in the intermediate lobe depends on the color of the background. In the lobe, two structurally different POMC proteins are produced from two mRNAs that are transcribed to approximately the same level from two POMC genes (A and B). We previously reported the entire nucleotide sequence of Xenopus POMC gene B. To identify conserved-- and thus potential regulatory--DNA elements in the Xenopus POMC gene, we here report the determination and analysis of the complete nucleotide sequence of Xenopus POMC gene A and its 5'- and 3'-flanking regions. Comparison of the two Xenopus POMC genes revealed, in addition to the exons, three highly conserved regions. First, the promoter regions are greater than 90% identical. The second region concerns JH12 repetitive elements situated at approximately the same position in both genes. These elements are greater than 86% identical. The third region is a 500-bp sequence just upstream of exon three (63% identity). Besides these three large regions, several small regions with significant identity were found at similar positions in the two POMC genes. The fact that, except for the JH12 element, the repetitive elements are not conserved between the two POMC genes indicates that these repeats are not functionally important.
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PMID:Comparative structural analysis of the transcriptionally active proopiomelanocortin genes A and B of Xenopus laevis. 158 15


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