Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proopiomelanocortin (POMC) is a precursor protein that contains the sequences of several bioactive peptides including adrenocorticotropin (ACTH), beta-endorphin (beta-EP), and melanocyte-stimulating-hormone (MSH). POMC is synthesized in the pituitary gland, brain, and many peripheral tissues. Immunoreactive POMC-derived peptides as well as POMC-like mRNA have been evidenced in several nonpituitary tissues, thus suggesting that POMC is actively synthesized by these tissues. The present study was aimed at evaluating if also in the case of stallion POMC-derived peptide, beta-EP, is produced locally in the testis, thus playing effects in a paracrine/autocrine fashion. To investigate this hypothesis the POMC gene expression was analyzed using 3' RACE-PCR and Northern Blot approaches in the testis and epididimys of stallion; moreover, immunocytochemical localization for beta-EP was also performed through confocal laser microscopy. The immunofluorescence results showed a positive beta-EP reaction not only in cellular nest of pituitary but also in the testis and genital tract of stallion, which function could be related with sperm mobility. Such role seem not to be no dependent on the peptide synthesized locally, because the molecular biology approach demonstrated the presence of POMC transcript in the pituitary only. In fact the Northern Blot analysis showed the presence of a single POMC transcript in the pituitary while no signal was detected in the testis and epididimys. The same results were obtained by applied 3' RACE-PCR analysis. In conclusion, opioid-derived peptide beta-EP is present in the genital tract of stallion, but is not locally produced as in other mammalian, and nonmammalian models; its possible biological function at testicular level could be linked to a long-loop feed-back mechanisms.
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PMID:Proopiomelanocortin gene expression and beta-endorphin localization in the pituitary, testis, and epididymis of stallion. 1617 84

Proopiomelanocortin (POMC) is a common precursor of adrenocorticotropic hormone (ACTH), melanophore-stimulating hormone (MSH), and endorphin (END). In pituitary gland, POMC receives posttranslational processing by which different peptides are generated in the pars distalis (PD) and pars intermedia (PI). Recently, we cloned three subtypes of the POMC gene in pituitary gland of barfin flounder. The present study was undertaken to elucidate whether the three POMC genes are expressed in both the PD and PI of barfin flounder pituitary, and to identify peptides derived from POMCs in these lobes. We amplified the transcripts of POMC-A, -B and -C in both the PD and PI by the reverse transcription-polymerase chain reaction. In situ hybridization also detected signals for these three subtypes in the PD and PI. These results demonstrated that all three POMC genes are expressed in both the PD and PI of barfin flounder pituitary. By mass spectrometric analyses, ACTH-A, Des-acetyl (Ac)-alpha-MSH-A/B (amino acid sequence of alpha-MSH-A is identical to that of alpha-MSH-B), beta-MSH-A, corticotropin-like intermediate lobe peptide (CLIP)-A, and N-terminal peptide (N-POMC)-A were identified in the PD. Moreover, Des-Ac-alpha-MSH-A/B, alpha-MSH-A/B, beta-MSH-A and -B, N-beta-lipotropin-A, CLIP-A, N-Ac-beta-END-A(1-41) (C-terminally truncated form of N-Ac-beta-END-A), and N-POMC-A were identified in the PI. Predominant detection of POMC-A-derived peptides indicates the greatest production of POMC-A and no detection of POMC-C-derived peptides indicates the lowest production of POMC-C in both the PD and PI. ACTH-A is specifically produced in the PD, however, the occurrence of Des-Ac-alpha-MSH-A, CLIP-A, and beta-MSH-A shows that the entire POMC-A is further cleaved into small peptides as in the PI. In the PI, some peptides receive modification or truncation as shown by the occurrence of alpha-MSH-A/B and N-Ac-beta-END-A(1-41). These results show differential posttranslational processing of POMC between the PD and PI in barfin flounder pituitary.
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PMID:Expression of three proopiomelanocortin subtype genes and mass spectrometric identification of POMC-derived peptides in pars distalis and pars intermedia of barfin flounder pituitary. 1624 90

Proopiomelanocortin (POMC) is a common precursor of melanocortin (MC), the collective term for adrenocorticotropic hormone (ACTH) and melanophore-stimulating hormone (MSH), and of beta-endorphin (beta-END). Over the past decade, considerable progress has been made in the analysis of the POMC gene from a board taxonomic group of vertebrates and invertebrates. The results suggest that three MSHs (alpha-, beta-, and gamma-MSH) and a single END were established in ancestral invertebrates. Thereafter, unequal crossing over may have resulted in class-specific numbers of MSH segments during the radiation of fish. Moreover, duplication of the entire POMC gene may have led to the differentiation of POMC as shown in lampreys; one of the two subtypes is a precursor for ACTH and beta-END, the other is a precursor for two forms of MSH and the other form of beta-END. On the other hand, at least five subtypes of MC receptor (MCR) have been observed in fish. These are G-protein-coupled receptors with seven transmembrane domains. The ancestral MCR is suggested to have appeared before vertebrates, and then MCRs may have diverged by genome duplication and local duplication of each receptor gene during the evolution of vertebrates. They are distributed in many tissues in rather a subtype-specific manner and are responsible for a variety of biological functions. Thus, MC systems may have diverged by producing structurally different MC peptides from POMC and expressing MCR subtypes differing in ligand selectivity in a variety of tissues.
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PMID:Evolution of melanocortin systems in fish. 1628 82

Proopiomelanocortin (POMC) can be processed to ACTH and melanocortin peptides. However, processing is incomplete in some tissues, leading to POMC precursor release from cells. This study examined POMC processing in human skin and the effect of POMC on the melanocortin-1 receptor (MC-1R) and melanocyte regulation. POMC was secreted by both human epidermal keratinocytes (from 5 healthy donors) and matched epidermal melanocytes in culture. Much lower levels of alpha-MSH were secreted and only by the keratinocytes. Neither cell type released ACTH. Cell extracts contained significantly more ACTH than POMC, and alpha-MSH was detected only in keratinocytes. Nevertheless, the POMC processing components, prohormone convertases 1, 2 and regulatory protein 7B2, were detected in melanocytes and keratinocytes. In contrast, hair follicle melanocytes secreted both POMC and alpha-MSH, and this was enhanced in response to corticotrophin-releasing hormone (CRH) acting primarily through the CRH receptor 1. In cells stably transfected with the MC-1R, POMC stimulated cAMP, albeit with a lower potency than ACTH, alpha-MSH, and beta-MSH. POMC also increased melanogenesis and dendricity in human pigment cells. This release of POMC from skin cells and its functional activity at the MC-1R highlight the importance of POMC processing as a key regulatory event in the skin.
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PMID:Proopiomelanocortin (POMC), the ACTH/melanocortin precursor, is secreted by human epidermal keratinocytes and melanocytes and stimulates melanogenesis. 1731 24

Proopiomelanocortin-producing neurons in the arcuate nucleus of the hypothalamus secrete beta-endorphin (beta-EP), which controls varieties of body functions including the feedback regulation of the CRH neuronal activity in the paraventricular nucleus of the hypothalamus. Whether ethanol exposure in developing rats induces beta-EP neuronal death and alters their influence on CRH neurons in vivo has not been determined. We report here that binge-like ethanol exposures in newborn rats increased the number of apoptotic beta-EP neurons in the arcuate nucleus of the hypothalamus. We also found that immediately after ethanol treatments there was a significant reduction in the expression of proopiomelanocortin and adenylyl cyclases mRNA and an increased expression of several TGF-beta1-linked apoptotic genes in beta-EP neurons isolated by laser-captured microdissection from arcuate nuclei of young rats. Several weeks after the ethanol treatment, we detected a reduction in the number of beta-EP neuronal perikarya in arcuate nuclei and in the number of beta-EP neuronal terminals in paraventricular nuclei of the hypothalamus in the treated rats. Additionally, these rats showed increased response of the hypothalamic CRH mRNA to the lipopolysaccharide challenge. The ethanol-treated animals also showed incompetent ability to respond to exogenous beta-EP to alter the lipopolysaccharide-induced CRH mRNA levels. These data suggest that ethanol exposure during the developmental period causes beta-EP neuronal death by cellular mechanisms involving the suppression of cyclic AMP production and activation of TGF-beta1-linked apoptotic signaling and produces long-term structural and functional deficiency of beta-EP neurons in the hypothalamus.
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PMID:Alcohol exposure during the developmental period induces beta-endorphin neuronal death and causes alteration in the opioid control of stress axis function. 1734 8

Proopiomelanocortin processing in corticotroph cells is known to be operated by prohormone convertase (PC) 1/3 which is activating several pro-proteins and prohormones by intracellular limited proteolysis processing. In this study, we hypothesized that PC1/3 expression differs between Cushing's disease (CD) and silent corticotroph adenoma (SCA), and investigated whether PC1/3 expression is involved in the adrenocorticotropin (ACTH) silence of SCA. We performed immunohistochemical analysis of pituitary adenoma specimens for six adenohypophysial hormones, PC1/3 and chromogranin A (CgA). Subjects for this study consisted of 12 anterior pituitary adenomas of CD (1 male, 11 female; 14-70 years old) and 31 non-functioning adenomas (23 male, 8 female; 32-71 years old).ACTH immunoreactivity was observed in all of CD and three of 31 non-functioning adenomas. The three cases diagnosed as SCA were also positive for growth hormone and follicle-stimulating hormone. Cushing's adenomas and SCAs were all positive for PC1/3. PC1/3-positive cells did not always colocalize with ACTH but some of them colocalized with CgA in SCAs. Even if PC1/3 is not present in corticotroph cells, PC1/3 immunoreactivity in SCA may originate from CgA-positive cells. We conclude that immunohistochemistry for PC1/3 is not helpful for differential diagnosis between CD and SCA in clinical practice, though the regulation of PC1/3 expression is likely to be an important etiological factor in ACTH silence of SCA. The diversity of immunohistochemical properties of SCA leads us to speculate that it is not a single entity and may be a general diagnostic term for adenomas of varying etiology.
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PMID:Immunohistochemical properties of silent corticotroph adenoma and Cushing's disease. 1741 Apr 13

Proopiomelanocortin (POMC) is the precursor of melanocyte-stimulating hormone (MSH) and beta-endorphin, and is suggested to have evolved by the insertion and deletion of ancestral MSH segments. Here, the primary structure of POMC was determined with cDNA cloning of brown tree snakes of Squamata and American alligators of Crocodylia to show an overview of the molecular evolution of POMC in reptiles. Snake and alligator POMCs are composed of alpha-, beta-, and gamma-MSH segments and a single beta-END segment as in other tetrapods; however, the gamma-MSH segment in snake POMC has a mutation in the essential sequence from His-Phe-Arg-Trp to His-(d)-(d)-Arg, in which (d) means deletion. It is conceivable that the ancestry of snake gamma-MSH had weak functional constraint and lacked biological significance during evolution. Phylogenetic analyses using the neighbor-joining method show that snake prePOMC is most diverged, and alligator prePOMC is most conserved in reptilian POMCs while it shows the highest sequence identity with ostrich prePOMC. These relationships are comparable to those observed in mitochondrial DNA. On the other hand, analyses of the pituitary with mass spectrometry revealed several peptides by post-translational processing as predicted by the locations of processing sites consisting of basic amino acid residues in snake and alligator POMCs. Remarkably, the monobasic site at the N-terminal side of the snake beta-MSH is suggested to act as a processing site. Thus, the study shows the divergence of snake POMC such as the critical mutation of gamma-MSH and high conservation of hormone organization of alligator POMC.
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PMID:cDNA cloning of proopiomelanocortin (POMC) and mass spectrometric identification of POMC-derived peptides from snake and alligator pituitaries. 1741 42

Anorexia and involuntary weight loss are common and debilitating complications of a number of chronic diseases and inflammatory states. Proinflammatory cytokines, including IL-1 beta, are hypothesized to mediate these responses through direct actions on the central nervous system. However, the neural circuits through which proinflammatory cytokines regulate food intake and energy balance remain to be characterized. Here we report that IL-1 beta activates the central melanocortin system, a key neuronal circuit in the regulation of energy homeostasis. Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) were found to express the type I IL-1 receptor. Intracerebroventricular injection of IL-1 beta induced the expression of Fos protein in ARC POMC neurons but not in POMC neurons in the commissural nucleus of the tractus solitarius. We further show that IL-1 beta increases the frequency of action potentials of ARC POMC neurons and stimulates the release of alpha-MSH from hypothalamic explants in a dose-dependent fashion. Collectively, our data support a model in which IL-1 beta increases central melanocortin signaling by activating a subpopulation of hypothalamic POMC neurons and stimulating their release of alpha-MSH.
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PMID:Regulation of central melanocortin signaling by interleukin-1 beta. 1752 25

Proopiomelanocortin (POMC) is processed in an intracellular secretory pathway, primarily to enable release of ACTH from the pituitary and alpha-MSH from hypothalamic neurons and skin. However, processing is incomplete and unprocessed POMC is secreted from all three tissues. This review considers intracellular processing of neuronal POMC as a key checkpoint that controls flux through hypothalamic melanocortin receptor pathways. Regulation of the convertase, proprotein convertase (PC)-1/3, which cleaves POMC is likely to determine the extent of POMC processing. Reduced PC1/3 activity, in both humans and rodents, leads to reduced melanocortin signaling and hence obesity. In contrast to POMC, posttranslational processing of proagouti-related peptide, an endogenous melanocortin-4 receptor antagonist, is efficient and is unlikely to represent a regulatory checkpoint. Because POMC is fully processed to ACTH and MSH peptides in secretory vesicles, unprocessed POMC, which is released from cells, must exit via an unregulated constitutive pathway. Therefore, the targeting of POMC to secretory granules controls the extent of POMC cleavage. There is evidence that PC1/3 is involved in cleavage of POMC in the trans-Golgi network and regulation of trafficking to the secretory pathway, in which it subsequently cleaves POMC to the melanocortin peptides. This would suggest that alpha-MSH and beta-MSH may be subject to alternative sorting mechanisms, leading to heterogeneity in secretory granule content in POMC-producing cells. Overall, these studies implicate POMC processing as a key regulatory mechanism in the control of energy homeostasis.
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PMID:Neuropeptide processing and its impact on melanocortin pathways. 1758 64

Proopiomelanocortin (POMC) is cleaved into small peptides, such as adrenocorticotropic hormone (ACTH), melanocyte-stimulating hormones (MSHs), and beta-endorphin (beta-END), by tissue-specific posttranslational processing in the corticotrophs of the pars distalis (PD) and melanotrophs of the neurointermediate lobe (NIL) of the pituitary. We examined the posttranslational processing of POMC in the pituitary of the banded houndshark Triakis scyllium by molecular cloning and subsequent mass spectrometric identification of the POMC-derived peptides in the pituitary extracts. One-fifth of the randomly selected clones from a Triakis pituitary cDNA library contained a cDNA encoding for POMC. Triakis prePOMC contained 4 MSHs and a single beta-END, as has been observed in case of other cartilaginous fish POMCs. These predicted hormonal segments were flanked by basic amino acid residues, which are the cleavage sites for the processing enzymes, i.e., protein convertases. Mass spectrometry was performed using PD (including most parts of the rostral and proximal PD) and NIL extracts to detect mass values corresponding to the POMC-derived peptides. Consequently, ACTH, beta-END, and the joining peptide (JP) were detected in the PD extract, while MSHs, processed beta-END, and some other POMC-derived peptides were identified in the NIL extract; however, neither acetylated alpha-MSH nor acetylated beta-END was detected in the latter. These tissue-specific POMC processing patterns are similar to those of the other vertebrate pituitaries; however, the absence of acetylated peptides suggests the lack of an acetylation system in the melanotrophs in the NIL of the Triakis pituitary.
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PMID:Evaluation of posttranslational processing of proopiomelanocortin in the banded houndshark pituitary by combined cDNA cloning and mass spectrometry. 1839 85


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