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)

The development of shock initiates a cascade of responses in an effort to reestablish homeostasis. Three of the most important hormonal and neurohumoral changes are the secretion of glucocorticoids, catecholamines, and vasopressin. Regulation of adrenal function is much more complex than originally thought. Hemorrhage is a potent stimulus for cortisol release, and both ACTH and ACTH-independent mechanisms have been described. The ACTH response to its releasing hormone, corticotropin releasing hormone (CRF), is itself amplified by vasopressin, which appears to have intrinsic CRF properties. Because ACTH is synthesized as part of a large precursor molecule (pro-opiomelanocortin) containing the amino acid sequences for several important proteins, stimulation of ACTH release has far-ranging effects, the specifics of which are just being clarified. Norepinephrine and epinephrine levels increase manyfold above baseline within minutes of the onset of hemorrhagic shock. Only patients experiencing cardiac arrest or the rare patient with a very active pheochromocytoma have higher concentrations. The levels reached are far in excess of those required to cause both cardiovascular and metabolic alterations. Because of the presence of the endogenous opiates leucine and methionine enkephalin in the neurosecretory granule, it is very likely that the enkephalins are coreleased with the catecholamines, modifying their cardiovascular effects and producing analgesia. Hypovolemia is also a potent stimulus for vasopressin secretion, which overrides hypotonicity, presenting a clinical picture quite compatible with the syndrome of inappropriate antidiuretic hormone secretion, from which it must be differentiated. Vasopressin also is released by pain, nausea, and hypoxia, all of which are likely to be present in the patient with shock.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endocrinology of shock. 353 88

Tissue contents of immunoreactive met-enkephalin (Met-Enk), leu-enkephalin (Leu-Enk) and met-enkephalin-Arg-Gly-Leu (Met-Enk-AGL) were determined by specific RIAs in 17 pheochromocytomas and the levels of preproenkephalin A mRNA were compared in some of these tissues by Northern blot hybridization. Remarkably wide distributions in the amounts of immunoreactive Met-Enk, Leu-Enk and Met-Enk-AGL were observed in 17 pheochromocytomas. Medullary pheochromocytomas contained significantly larger amounts of immunoreactive Met-Enk, Leu-Enk and Met-Enk-AGL than did the extramedullary ones. Significant positive correlations of tumor tissue immunoreactivities between Met-Enk and Leu-Enk (r = 0.97, P less than 0.01) and between Met-Enk and Met-Enk-AGL (r = 0.97, P less than 0.01) were observed. No difference in size of mRNA of preproenkephalin A was observed in the pheochromocytomas. Medullary pheochromocytomas contained higher amounts of preproenkephalin A mRA than did the extramedullary ones. The quantities of preproenkephalin A mRNA in nine pheochromocytoma tissues significantly correlated with those of immunoreactive Met-Enk in these tissues (r = 0.94, P less than 0.01). These results indicate that the remarkable difference in tissue immunoreactivities of preproenkephalin A-derived opioid peptides is decided at the transcriptional level but not at the posttranslational level.
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PMID:Preproenkephalin A-derived opioid peptides and mRNA of preproenkephalin A in human pheochromocytomas. 359 3

We studied the secretion and tissue contents of adrenorphin in human pheochromocytomas. In 17 human pheochromocytomas from 11 patients, we found a remarkably wide distribution in immunoreactive adrenorphin levels (3-7771 pg/mg tissue). Adrenomedullary pheochromocytomas contained a significantly larger amount of immunoreactive adrenorphin (2295 +/- 1092 pg/mg, mean +/- SE) than did extramedullary ones (17.8 +/- 8.4 pg/mg). Gel chromatographic studies revealed that immunoreactive adrenorphin consisted largely of material emerging at the position of synthetic adrenorphin in both pheochromocytoma and normal adrenal medulla tissue. Nicotine (10(-5) M) significantly stimulated the secretion of immunoreactive adrenorphin as well as catecholamines from cultured human pheochromocytoma cells. Adrenorphin was a more potent inhibitor of catecholamine secretion evoked by 10(-5) M nicotine than was met-enkephalin in cultured human pheochromocytoma cells. The 50% inhibitory concentrations (IC50) were 1.1 X 10(-6) and 6.5 X 10(-5) M for adrenorphin and met-enkephalin, respectively. The effect of adrenorphin was much the same as that of dynorphin-(1-13) (IC50, 1.0 X 10(-6) M) and BAM-12P (IC50, 4.5 X 10(-6) M). These results indicate the presence and secretion of adrenorphin in human pheochromocytomas. Adrenorphin may play an important role in regulating catecholamine secretion in human pheochromocytoma.
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PMID:Studies on adrenorphin in pheochromocytoma. 381 99

Corticotropin-releasing factor (CRF)-like immunoreactivity was measured by radioimmunoassay in human organs and tumors associated with and without ectopic adrenocorticotropic hormone (ACTH) syndrome. It was found to be distributed widely in the stomach, pancreas, adrenal gland, and various tumors (e.g., medullary thyroid carcinoma, small cell carcinoma of the lung, pheochromocytoma, and adenocarcinoma of the gastrointestinal tract and pancreas) in a concentration less than one tenth of that of the hypothalamus. Dilution curves of CRF-like immunoreactivity in tissue extracts paralleled that of synthetic rat (human) CRF. Sephadex G-50 gel filtration showed that a major CRF-like immunoreactivity in tissue extracts coeluted with synthetic rat (human) CRF. Results suggest that a material(s) closely related immunologically to CRF is present widely in normal and tumor tissues outside of the central nervous system.
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PMID:Presence of corticotropin-releasing factor-like immunoreactivity in human tumors. 387 47

The concentration of epinephrine, norepinephrine, dopamine, met-enkephalin-, ACTH-, calcitonin- and somatostatin-like immunoreactivity (IR) were determined in the extracts of 9 adrenal pheochromocytomas from 7 patients. Six of these patients had Sipple's syndrome. There was a close correlation between the amounts of met-enkephalin-IR and of epinephrine present in the tumor tissue (p less than 0.01). Such a correlation was not found between catecholamines and the other polypeptide hormones investigated. The relevance of the close parallel in the occurrence of met-enkephalin-IR and epinephrine in human adrenal pheochromocytoma tissue is unknown, but it underlines earlier observations in the normal bovine and rat adrenal medulla on a co-storage and co-release of these substances in normal circumstances.
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PMID:A close correlation between the amount of met-enkephalin-immunoreactivity and epinephrine in adrenal pheochromocytoma tissue from patients with Sipple's syndrome. 614 10

Cushing's syndrome in association with a tumor of the autonomic nervous system (ANS) has been reported occasionally. We studied a patient who had an intra-adrenal paraganglioma (pheochromocytoma), and whose plasma corticotropin level was elevated prior to surgery but dropped to a low value following removal of the tumor. Catecholamine levels were elevated preoperatively and catecholamines were extracted from the tumor tissue. Corticotropin was identified in the tumor by immunoperoxidase staining. We also compared the endocrine data of 16 previously reported cases of Cushing's syndrome secondary to the release of ectopic corticotropin from ANS tumors. We concluded that in these patients, the plasma corticotropin level is only modestly elevated but indexes of steroid production frequently are markedly elevated. Also, discrepant responses to dexamethasone suppression tests occur, perhaps via sporadic release of corticotropin. These factors complicate evaluation of the cause of Cushing's syndrome in these patients.
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PMID:Corticotropin production by tumors of the autonomic nervous system. 632 25

Plasma methionine-enkephalin-like and leucine-enkephalin-like immunoreactivity (met-enkephalin-LI and leu-enkephalin-LI, respectively) in six normal subjects and six patients with pheochromocytoma were determined. The contents of met-enkephalin-LI and leu-enkephalin-LI in two of six pheochromocytomas were 40- to 50-fold higher and those in the other four pheochromocytomas were less than those in normal human adrenal medulla. The former two patients showed high plasma met-enkephalin-LI and leu-enkephalin-LI levels. As plasma catecholamines levels returned to the normal range after extirpation of tumors, met-enkephalin-LI and leu-enkephalin-LI in plasma became undetectable in these patients. In contrast, neither met-enkephalin-LI nor leu-enkephalin-LI was detected in plasma from the latter four patients. Met-enkephalin-LI and leu-enkephalin-LI concentrations were higher in the adrenal vein than in the peripheral vein in three patients. Plasma met-enkephalin-LI and leu-enkephalin-LI increased concomitantly with catecholamines after glucagon stimulation and during a spontaneous attack in a patient with pheochromocytoma. Plasma met-enkephalin-LI changed in parallel with leu-enkephalin-LI in all cases. High performance liquid chromatography coupled with RIAs has shown that met-enkephalin and leu-enkephalin circulate in plasma from a patient with pheochromocytoma as intact pentapeptides. None of normal subjects showed detectable concentrations of met-enkephalin-LI and leu-enkephalin-LI in plasma (more than 5 pg/ml and 3 pg/ml, respectively). It is concluded that met-enkephalin and leu-enkephalin are released concomitantly with catecholamines from pheochromocytomas.
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PMID:Plasma methionine-enkephalin and leucine-enkephalin in normal subjects and patients with pheochromocytoma. 688 62

[Met]enkephalin and [Leu]enkephalin are derived from a protein in bovine adrenal medulla that contains multiple copies of [Met]enkephalin [Kilpatrick, D. L., Taniguchi, T., Jones, B. N., Stern, A. S., Shively, J. E., Hullihan, J., Kimura, S., Stein, S. & Udenfriend, S. (1981) Proc. Natl. Acad. Sci. USA 78, 3265--3268.] Here we characterize pro-enkephalin mRNA from bovine and human tissue by use of an oligodeoxynucleotide pentadecamer probe complementary to codons for Tyr-Gly-Gly-Phe-Met ([Met]enkephalin). This probe hybridizes specifically to a species of poly(A)-RNA from adrenal medulla and human pheochromocytoma, (1400--1450 bases), and also to [Met]enkephalin-containing pro-opiomelanocortin mRNAs from bovine pituitary (1200 bases) and from mouse pituitary tumor cell (1100 bases). A cloned cDNA probe (144 bases) complementary to the region of pro-opiomelanocortin mRNA that codes for lipotropin does not hybridize to the RNA from bovine adrenal medulla, demonstrating that the latter RNA is not pro-opiomelanocortin mRNA. The pentadecamer probe was extended to make cDNA with reverse transcriptase after hybridizing it to adrenal poly(A)-RNA. The sequence of an extended cDNA, 62 bases in length, was found to correspond exactly to that expected from the amino acid sequence of peptide E (a bovine adrenal peptide containing [Met]- and [Leu]enkephalin sequences). This cDNA also forms a specific hybrid with the RNA from bovine adrenal and human pheochromocytoma, confirming that these species of RNA are pro-enkephalin mRNA.
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PMID:Partial characterization of the mRNA that codes for enkephalins in bovine adrenal medulla and human pheochromocytoma. 695 89

The potent hypotensive peptide, adrenomedullin (AdM), originally isolated from a human pheochromocytoma is present in a variety of rat and human tissues. We examined its potential effects in anterior pituitary gland, reasoning that it may be a feedback regulator of adrenocorticotropin (ACTH) secretion. Rat AdM11-50 inhibited basal ACTH secretion from dispersed, rat anterior pituitary cells in a significant, dose-related fashion (maximum inhibition at 10(-9) M). Rat AdM11-50 also inhibited, in a dose-related fashion, corticotropin releasing hormone (CRH)-stimulated ACTH secretion, but did not block the ability of CRH to stimulate cAMP accumulation in these cells. These findings suggest that in addition to peripheral actions in the vasculature and kidney, adrenomedullin may act within the anterior pituitary gland to control fluid and electrolyte homeostasis.
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PMID:A novel vasoactive peptide, adrenomedullin, inhibits pituitary adrenocorticotropin release. 772 Jun 84

A pheochromocytoma from a 59-year-old woman was found to be immunoreactive to adrenocorticotropin (ACTH), chromogranin, neurofilament-200, neuron-specific enolase and S-100 protein. Northern blot analysis showed that both proopiomelanocortin (POMC) and corticotropin-releasing hormone (CRH) genes were expressed in the pheochromocytoma but not in the surrounding adrenal cortex. In primary culture, the POMC and CRH mRNAs were increased by dexamethasone (500 micrograms/l for 3 days) up to 10- and 15-fold of the control, respectively. The secretion of ACTH also was stimulated eightfold with the same treatment. The stimulatory effect of dexamethasone on POMC gene expression was inhibited 70% by nerve growth factor (NGF, 200 micrograms/l), 30% by 12-O-tetradecanoyl phorbol 13-acetate (TPA, 160 nmol/l) (a protein kinase-C activator) and 30% by (Bu)2cAMP (1 mmol/l). On the other hand, NGF alone increased the CRH mRNA accumulation up to 10-fold, and further enhanced the stimulatory effect of dexamethasone on the CRH mRNA twofold, and TPA inhibited (30%) the dexamethasone-induced CRH mRNA accumulation. Furthermore, the conditioned medium of the pheochromocytoma cells increased secretion of corticosterone fourfold in the primary culture of rat fetal adrenal cells. Our results indicate abnormal expression and regulation of POMC and CRH genes in this pheochromocytoma.
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PMID:Pheochromocytoma expressing adrenocorticotropin and corticotropin-releasing hormone; regulation by glucocorticoids and nerve growth factor. 792 Dec 4


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