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 production and secretion of peptides by adrenocortical tumors have not been well studied. We therefore studied the production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1 in SW-13 human adrenocortical carcinoma cells by radioimmunoassay and Northern blot analysis. Both immunoreactive-adrenomedullin and immunoreactive-endothelin were detected in the culture medium of SW-13 cells (27.7 +/- 1.6 fmol/10 (5) cells/24 h and 11.0 +/- 0.8 fmol/10 (5) cells/24 h, respectively, mean +/- SEM, n = 6). Northern blot analysis showed the expression of adrenomedullin mRNA and endothelin-1 mRNA in SW-13 cells. On the other hand, no significant amount of calcitonin gene-related peptide, corticotropin-releasing hormone, neuropeptide Y, or urocortin was secreted by SW-13 cells. Treatment with ACTH (10(-9)-10(-7) mol/l), angiotensin II (10(-9)-10(-7) mol/l), or dexamethasone (10(-8)-10(-6) mol/l) for 24 h had no significant effects on immunoreactive-adrenomedullin levels and immunoreactive-endothelin levels in the culture medium of SW-13. Treatment with tumor necrosis factor (TNF)-alpha (20 ng/ml) increased significantly both immunoreactive-adrenomedullin levels and immunoreactive-endothelin levels in the culture medium. Interferon-gamma (100 U/ml) increased the immunoreactive-endothelin levels, but not immunoreactive-adrenomedullin levels, whereas interleukin-1 (IL-1)beta (10 ng/ml) increased immunoreactive-adrenomedullin levels, but not immunoreactive-endothelin levels. These findings indicate that SW-13 human adrenocortical carcinoma cells produce and secrete two vasoactive peptides, adrenomedullin, and endothelin-1 and that the secretion of these two peptides is modulated differently by cytokines.
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PMID:Production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1, by cultured human adrenocortical carcinoma cells. 1076 53

The investigation was conducted to study the effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on adrenocorticotropin (ACTH), cortisol and prolactin release in man. The design was a prospective placebo controlled double-blind study, including 7 healthy males studied on three occasions. After infusion of either 20 ng/min x kg ET-1, ET-3 or normal saline, venous blood samples were drawn 12 times for determination of ACTH, cortisol and prolactin during the pre- within- and postinfusion period. ET-1 infusion induced a significant increase of plasma ACTH (p< 0.009) and prolactin (p<0.0001) whereas cortisol levels increased without reaching significance (p<0.074). Infusion of ET-3 induced no changes in plasma levels of ACTH, cortisol or prolactin. The parallel increase of ACTH and prolactin induced by infusion of ET-1 could indicate an involvement of corticotropin-releasing hormone (CRH) in mediating the ET-1 effect on the HPA-axis in man. Whether this supports a possible role of ET-1 as a modulator of the hypothalamo-pituitary-adrenal (HPA) axis remains to be clarified.
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PMID:Comparison of the effects of endothelin-1 and -3 on secretion of pituitary hormones in healthy male volunteers. 1098 58

Orexins A and B are two hypothalamic peptides that increase food intake and body weight and probably play a role in the sleep regulation. They act through two subtypes of G protein-coupled receptors, called OX1-R and OX2-R. OX1-R selectively binds orexin-A, whereas OX2-R is nonselective for both orexins. Orexins did not affect the in vitro secretion of either catecholamine or aldosterone from human adrenals. Conversely, orexin A, but not orexin B, concentration dependently increased basal cortisol secretion from dispersed adrenocortical cells; the maximal effective concentration was 10(-8) mol/L. Orexin A (10(-8) mol/L) enhanced the cortisol response to maximal effective concentrations (10(-9) mol/L) of angiotensin II and endothelin-1, but only to low concentrations of ACTH (10(-12)/10(-11) mol/L). Orexin A (10(-8) mol/L) increased basal cAMP release by dispersed adrenocortical cells, and the effect was blocked by the adenylate cyclase inhibitor SQ-22536. The cortisol response to 10(-8) mol/L orexin A was unaffected by the ACTH receptor antagonist corticotropin-inhibiting peptide, but was abolished by either SQ-22536 or the protein kinase A inhibitor H-89. RT-PCR demonstrated high levels of OX1-R messenger ribonucleic acid and very low levels of OX2-R messenger ribonucleic acid in human adrenal zona fasciculata-reticularis and adrenal medulla. Collectively, our findings suggest that orexins selectively stimulate glucocorticoid secretion from human adrenocortical cells, acting through OX1-R coupled with the adenylate cyclase-dependent signaling pathway.
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PMID:Orexin A stimulates cortisol secretion from human adrenocortical cells through activation of the adenylate cyclase-dependent signaling cascade. 1115 46

In the last several decades, the concept of "endocrinology" has been greatly changed. One major change was due to the discovery of peptide hormones secreted by the organs that were not "classical" endocrine organs. For example, corticotropin-releasing hormone and many neuropeptides are secreted by the neurons, atrial natriuretic peptide by the heart, endothelin-1 by the vascular endothelial cells, and leptin by the adipose tissues. Now, the brain, heart, vascular tissue and adipose tissue can be considered to be endocrine organs. Cardiovascular diseases and obesity are therefore important targets of the endocrine research. Adrenomedullin is a potent vasodilator peptide consisting of 52 amino acids. It was originally discovered from a human pheochromocytoma, and belongs to the calcitonin gene-related peptide (CGRP) family. Adrenomedullin is produced and secreted by various types of cells, for example, vascular endothelial and smooth muscle cells, cardiomyocytes, fibroblasts, macrophages, neurons, glial cells, and retinal pigment epithelial cells. Such ubiquitous expression has not been observed in other neuropeptides, including neuropeptide Y and CGRP. Expression of adrenomedullin is induced by hypoxia and proinflammatory cytokines. In addition to vasodilator actions, this peptide has central inhibitory actions on water drinking and salt appetite, effects on the secretion of some hormones and cytokines, inotropic actions and effects on cell growth and apoptosis. Adrenomedullin is produced by various non-endocrine tumors, as well as endocrine tumors, and acts as a growth stimulatory factor for the tumor cells. Adrenomedullin seems to be involved in the pathophysiology of many diseases, including ischemic heart diseases, inflammatory diseases, tumors, and even eye diseases. The adrenomedullin research implies that "the neuroendocrine system" exists in much broader types of cells than previously thought, and that the endocrine research is able to contribute to the understanding of the pathophysiology of many diseases.
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PMID:Adrenomedullin from a pheochromocytoma to the eye: implications of the adrenomedullin research for endocrinology in the 21st century. 1131 31

Adrenomedullin, a potent vasoactive peptide, is actively secreted from primary cultures of human oral and skin keratinocytes, but nothing is known of the regulation of its release. This study describes the effects of a range of substances on adrenomedullin production from cultures of oral and skin keratinocytes. We have established that keratinocytes do not store adrenomedullin but secrete it constitutively. Cytokines interleukin-1alpha and -1beta, tumor necrosis factor-alpha and -beta, and the bacterial product, lipopolysaccharide, significantly stimulate adrenomedullin secretion from oral but not skin keratinocytes. Both transforming growth factor-beta1 and interferon-gamma are potent suppressors of adrenomedullin secretion from both cell types, as are forskolin, di-butyryl cyclic adenosine monophosphate, and adrenocorticotropin. The peptides thrombin and endothelin-1 increase adrenomedullin production, particularly from skin keratinocytes. These findings indicate that there are differences in the regulation of adrenomedullin production between oral and skin keratinocytes and that oral keratinocytes are particularly responsive to the action of inflammatory cytokines. This raises the possibility that adrenomedullin may serve a different functions in oral mucosa and skin.
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PMID:Regulation of adrenomedullin secretion in cultured human skin and oral keratinocytes. 1151 15

Urocortin (Ucn) is a member of the corticotropin-releasing hormone (CRH)-related peptides that has been reported to have cardiac inotropic and hypertrophic effects. In addition, Ucn mRNA was expressed in cardiac myocytes (MCs) and Ucn was suggested to have cardioprotective effects. Recently, it was reported that Ucn mRNA was expressed in cardiac non-myocytes (NMCs). Based on these facts, Ucn is assumed to affect not only MCs but also NMCs in an autocrine fashion. The present study was designed to elucidate a pathophysiological role of Ucn on NMCs. NMCs were prepared by the discontinuous Percoll gradient and adhesion method. Ucn increased [(3)H]-thymidine uptake into NMCs. Ucn also enhanced endothelin-1-induced increase of [(3)H]-thymidine uptake into NMCs. Effects of Ucn on [(3)H]-thymidine uptake into NMCs were significantly abolished by the protein kinase A inhibitor, H89 (10(-5) M), but not by a competitive antagonist of CRH receptors, astressin (10(-5) M). Ucn also increased intracellular cAMP accumulation more potently than CRH on a molar basis. Finally, both MCs and NMCs also secreted Ucn. Together with the recent findings, at least in NMCs, these data suggest that Ucn could exert its own actions via the cAMP signaling pathway, but not through known CRH type 2 receptors, in an autocrine fashion. In conclusion, the present study indicated that Ucn was secreted not only from MCs but also from NMCs and that the primary source of Ucn acting on heart was the heart itself. On the other hand, Ucn could proliferate NMCs as well as MCs, suggesting that Ucn could be involved in cardiac hypertrophy and fibrosis, i.e., cardiac remodeling, in spite of its putative cardioprotective actions.
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PMID:Urocortin has cell-proliferative effects on cardiac non-myocytes. 1217 7

To evaluate the etiologic role of ultraviolet (UV) radiation in acquired dermal melanocytosis (ADM), we investigated the effects of UVA and UVB irradiation on the development and differentiation of melanocytes in primary cultures of mouse neural crest cells (NCC) by counting the numbers of cells positive for KIT (the receptor for stem cell factor) and for the L-3,4-dihydroxyphenylalanine (DOPA) oxidase reaction. No significant differences were found in the number of KIT- or DOPA-positive cells between the UV-irradiated cultures and the non-irradiated cultures. We then examined the effects of UV light on KIT-positive cell lines derived from mouse NCC cultures. Irradiation with UVA but not with UVB inhibited the tyrosinase activity in a tyrosinase-positive cell line (NCCmelan5). Tyrosinase activity in the cells was markedly enhanced by treatment with alpha-melanocyte-stimulating hormone (alpha-MSH), but that stimulation was inhibited by UVA or by UVB irradiation. Irradiation with UVA or UVB did not induce tyrosinase activity in a tyrosinase-negative cell line (NCCmelb4). Levels of KIT expression in NCCmelan5 cells and in NCCmelb4 cells were significantly decreased after UV irradiation. Phosphorylation levels of extracellular signal-regulated kinase 1/2 in cells stimulated with stem cell factor were also diminished after UV irradiation. These results suggest that UV irradiation does not stimulate but rather suppresses mouse NCC. Thus if UV irradiation is a causative factor for ADM lesions, it would not act directly on dermal melanocytes but may act in indirect manners, for instance, via the overproduction of melanogenic cytokines such as alpha-MSH and/or endothelin-1.
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PMID:Effects of ultraviolet light on melanocyte differentiation: studies with mouse neural crest cells and neural crest-derived cell lines. 1501 4

Twelve patients with chronic critical limb ischemia in whom a spinal cord stimulation (SCS) system had been implanted for at least one year had increased microvascular flow and achieved healing of trophic acral lesions. After switching off the system, the clinical improvement persisted for 10 days and the neurohormonal pattern showed high plasma values of beta-endorphin and Met-enkephalin, normal dynorphin B, endothelin-1 and catecholamines, and low nitric oxide. Met-enkephalin levels were further increased (P < 0.01) immediately after switching on the electrical stimulation again. The persistence of high plasma opioid levels after switching off the spinal cord stimulation explains the absence of subjective complaints and suggests an involvement of opioids in the regulation and improvement of the microcirculation.
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PMID:Opioid peptide response to spinal cord stimulation in chronic critical limb ischemia. 1516 11

Nitric oxide (NO) is a potent intercellular mediator of melanogenesis, whereas metallothionein (MT) is an inducible intracellular antioxidant that has been reported to scavenge NO. We investigated the existence and induction of MT in melanocytes, and its inhibitory effect on NO-induced melanogenesis. The expression of MT was detected in melanocytes, however, at a lower level than in keratinocytes, and its induction was possible by the addition of zinc chloride. Further, an NO-stimulated increase of tyrosinase activity in melanocytes was remarkably suppressed, when MT was induced prior to NO stimulation. Melanogenesis was also suppressed, when dexamethasone was used to induce MT. However, an NO-stimulated increase of tyrosinase expression was not suppressed at the gene and protein level, when MT was induced in melanocytes. The same suppressive effect of melanogenesis was also observed, when alpha-melanocyte-stimulating hormone or endothelin-1 was used as a stimulator. Because these results implied a mechanism other than NO scavenging to explain the suppressive effect of MT induction on melanogenesis, the direct inhibition of tyrosinase by MT was examined. Melanosome fractions were prepared from melanocytes, whose melanogenesis was suppressed by the induction of MT. Tyrosinase suppression was observed in the melanosome fractions, which was neutralized by the addition of anti-MT antibody. These results suggest that MT induction may be effective to suppress melanogenesis stimulated by NO as well as other melanogens, and these suppressive effects might be due to a direct inhibition of tyrosinase activity in melanosome and not a scavenging effect of NO.
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PMID:Suppression of melanogenesis by induction of endogenous intracellular metallothionein in human melanocytes. 1526 10

The aim was to assess the developmental and biochemical effects resulting from separate and combined exposures to radiation and noise in adult male Sprague-Dawley rats. For 21 days, animals were exposed daily (1) to whole-body 121 kVp X-ray exposure (cumulative dose=5 Gy), (2) to random intermittent noise band-limited between 0.4 and 20 kHz; 2 h day(-1) 86 decibels (dB) and (3) to combined exposures. Control animals were housed under ambient noise conditions 55 dB A-weighted (dBA) and sham-exposed to X-rays. Body weight gain was significantly reduced in animals exposed to either X-rays or noise, and the loss was more pronounced in animals exposed to both conditions. Neither plasma adrenocorticotropic hormone (ACTH) nor corticosterone was altered by the treatment conditions. This study corroborated previous reports that ionizing radiation exposure increased plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHDG), but no effect was observed in animals co-exposed to chronic noise. Plasma big-endothelin-1 (Big ET-1) was significantly reduced in animals exposed to a combination of noise and X-rays. The results indicated that (1) adaptation to chronic noise appeared to occur at the level of the hypothalamic pituitary adrenal (HPA) response, in spite of a compromise in overall body weight gain; and (2) ionizing radiation exposure might alter systems activated by stressor exposure and/or act independently to influence health outcomes.
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PMID:Exposure to chronic noise and fractionated X-ray radiation elicits biochemical changes and disrupts body weight gain in rat. 1601 39


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