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)

Immunohistochemical and biochemical analyses were performed on the pituitary Proopiomelanocortin (POMC) systems of the polypteriform fish Calamoichthys calabaricus. Immunohistochemical staining of the pituitary revealed a clustering of ACTH immunopositive cells within the rostral pars distalis. alpha-Melanocyte stimulating hormone (alpha-MSH)-related and beta-endorphin-related immunoreactivity were found colocalized in epithelial cells of the pars intermedia. Biochemical analyses included Sephadex G-50 column chromatography, reversed-phase HPLC, and cation exchange chromatography. These analyses revealed the presence of immunoreactive forms of ACTH which stimulated glucocorticoid release when tested on isolated Bufo marinus adrenocortical tissue. Three forms of alpha-MSH were detected, and the major form had the same HPLC chromatographic properties as synthetic monoacetylated alpha-MSH. Finally, five forms of beta-endorphin were detected, and all of these forms were N-acetylated. Based on these observations, it appears that N-acetylation is a major post-translational processing event within the melanotropic cells of C. calabaricus. Given the position of Order Cladistia in the phylogeny of actinopterygian fish, it appears that N-acetylation of POMC-related products is an ancestral trait of osteichthyean fish.
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PMID:An anatomical and biochemical study of the pituitary proopiomelanocortin systems in the polypteriform fish Calamoichthys calabaricus. 838 5

Proopiomelanocortin (POMC) is the precursor of the potent opioid peptide beta-endorphin as well as a number of other active peptides. On the basis of neuroanatomical data indicating the presence of contacts between POMC neurons in the rat arcuate nucleus, it has been proposed that POMC neurons could be autoregulated. In order to investigate the role of opiates in the regulation of POMC gene expression in the rat arcuate nucleus, we studied the effects of chronic administration of the opioid drug morphine and an opiate receptor antagonist naloxone on POMC mRNA levels as measured by in situ hybridization, 4-day treatment with naloxone (4 mg/kg/day) produced a 60% increase in the number of silver grains overlying POMC neurons. Conversely, morphine (40 mg/kg/day) also administered during 4 days decreased the hybridization signal by 30%. The concomitant administration of morphine and naloxone completely prevented the effect of morphine on POMC gene expression indicating that the inhibitory influence of morphine is likely to be mediated by opioid receptors. The data obtained clearly indicate that activation of opioid receptors decreased the biosynthetic activity of POMC neurons and that conversely opiate receptor blockade caused an increase in the activity of these neurons. They are consistent with the hypothesis of an autoregulation of the POMC neuronal system by endogenous opiate peptide(s).
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PMID:Opioid regulation of proopiomelanocortin (POMC) gene expression in the rat brain as studied by in situ hybridization. 841 62

Proopiomelanocortin (POMC)-producing cells comprise nearly 100% of the adult rat intermediate lobe (IL) hormone-producing cells. Secretion by these cells in the adult is primarily under negative regulation by dopamine. Although the POMC-derived peptide alpha-MSH has been detected in plasma of fetal rats, the secretory capability of fetal melanotrophs has not yet been examined directly. Here we have used the reverse hemolytic plaque assay to assess, at the single-cell level, basal and regulated release by melanotrophs from fetal and early postnatal ages. Basal secretion was detected at the earliest age examined [Embryonic Day 17.5 (e17.5)], but CRH (10(-8) M) stimulated secretion was not observed until e19.5. As development proceeded, CRH increased both individual plaque sizes and the percentage of melanotrophs stimulated to secrete. An unexpected, transient inhibition of CRH stimulated release from melanotrophs by dexamethasone (DEX, 10(-6) M) was observed from e19.5-p2 (postnatal Day 2). By p3, however, DEX no longer inhibited melanotroph secretion while inhibition of CRH-stimulated release from p3 corticotrophs was readily detected. The dopamine agonist ergocryptine (ERG, 10(-6) M) inhibited basal secretion from melanotrophs, but not corticotrophs, at all ages examined. Taken together, these results indicate that melanotrophs undergo a maturation process in which they are initially nonresponsive to CRH, next possess functional CRH and steroid receptors, and finally, undergo functional uncoupling of steroid receptors which characterizes the adult IL. The loss of steroid-mediated inhibition of stimulated secretion parallels the arrival of catecholaminergic input into the IL. In contrast, the early response of melanotrophs to dopaminergic agonists, which can be detected 1 week prior to arrival of catecholaminergic fibers into the neurointermediate lobe, appears to be an intrinsic feature of these cells that is never present in corticotrophs.
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PMID:Ontogeny of basal and regulated proopiomelanocortin-derived peptide secretion from fetal and neonatal pituitary intermediate lobe cells: melanotrophs exhibit transient glucocorticoid responses during development. 857 13

Proopiomelanocortin (POMC)-producing cells are present in both the anterior (AL) and intermediate (IL) lobes of the adult rat pituitary. Both cell types are derived from a single embryonic rudiment, Rathke's pouch, and synthesize the same hormone precursor, POMC, but differ in the pattern of precursor processing and regulation of peptide secretion. Here we have used the reverse hemolytic plaque assay to determine the ontogeny of basal and regulated secretion by AL POMC cells. Basal secretion of beta-endorphin was first observed at Embryonic Day 13.5 (e13.5), the age when POMC-derived peptides were first detected immunocytochemically. Peptide secretion stimulated by corticotropin releasing hormone (CRH; 10(-8) M) was first detected at e15.5. The CRH-stimulated secretion involved two different components: (1) an increase in the amount of hormone secreted per cell (increase in plaque size) as well as (2) an increase in the number of plaque-producing cells. The greatest stimulation by CRH was observed at e16.5, a time when AL POMC mRNA levels increase significantly and when CRH neurons are first detected immunocytochemically in the hypothalamus. CRH-stimulated secretion, but not basal release, was inhibited by preincubation with dexamethasone (DEX; 10(-6) M) as early as e15.5, while the dopamine agonist ergocryptine (ERG; 10(-6) M) did not alter basal or CRH-stimulated release at any age studied. These results demonstrate that AL POMC cells are capable of hormone secretion as early as POMC peptides are first detected immunocytochemically and that these cells respond in an adult-like manner to physiological regulators soon after their initial appearance. Moreover, these responses remain unaltered during the early postnatal stress-nonresponsive period, suggesting that deficits at this time must lie at a level other than the corticotroph. Taken together, these results show that AL POMC cells possess functional regulatory receptor systems prior to maturation of the hypothalamic-hypophyseal portal system.
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PMID:Ontogeny of basal and regulated secretion from POMC cells of the developing anterior lobe of the rat pituitary gland. 857 41

Proopiomelanocortin (POMC) is the precursor for adrenocorticotropic hormone, melanocyte-stimulating hormones, beta-lipotropic hormone (beta LPH), and beta endorphin. These peptides can function as neurotransmitters, modulate immune responses, and affect melanogenesis. We investigated POMC expression and protein processing in normal human keratinocytes. On Northern blot analysis, the baseline expression of the 1.2-kb POMC transcript was upregulated by ultraviolet radiation (UVR) or by stimulation with interleukin-1 alpha (IL-1 alpha) or phorbol 12-tetradecanoate 13-acetate (TPA). On Western blot analysis, POMC, beta LPH, and beta-endorphin were detected in cell extracts under baseline conditions. beta LPH level increased substantially after UVR, IL-1 alpha, or TPA. Within 36 h after TPA stimulation, beta-endorphin became undetectable in cell extracts, coinciding with an increase of beta-endorphin-immunoreactive protein in the culture medium. Our data establish that keratinocytes synthesize POMC protein as well as its derivatives beta LPH and beta-endorphin, and that this process is modulated by TPA, IL-1A, and UVR. beta LPH and beta-endorphin of keratinocyte origin may thus be involved in melanogenesis and/or immunomodulation in the skin after sun exposure, and their release into the circulation may also have systemic effects.
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PMID:Proopiomelanocortin gene product regulation in keratinocytes. 861 3

Proopiomelanocortin (POMC) is a neuropeptide precursor molecule which is translocated to the secretory pathway within neuroendocrine cells. It is cleaved by the action of endopeptidases to yield mature peptides like adrenocorticotrophic hormone (ACTH), beta-lipotrophin (beta-LPH), beta-endorphin. In this review we present evidence on the cleavage specificities and structure of endoproteases which cleave neuropeptide precursors at pairs of basic amino acids and on the identity and mode of action of exopeptidases. This information is derived from cloning of their corresponding cDNAs and subsequent expression within neuroendocrine cells; and also from biochemical studies. We discuss the intracellular targeting and sorting mechanisms of POMC within neuroendocrine cells. We also examine the tissue-specific post-translational processing of POMC within the anterior and intermediate lobes of the pituitary gland and within the central nervous system.
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PMID:Post-translational processing of proopiomelanocortin in the pituitary and in the brain. 909 13

To evaluate the role of Hypothalamic-Pituitary-Adrenal (HPA) hormones and psychoneuroendocrine modulation on NK cell activity in Anorexia Nervosa (AN) we studied in 24 patients and 20 sex- and age-matched healthy controls, the spontaneous NK activity of peripheral blood mononuclear (PBM) cells and the susceptibility in vitro to cortisol or immune interferon or interleukin-2. NK cytotoxicity of PBM cells was measured in a direct non-radiometric 4h cytolytic assay using K562 cells as targets. HPA axis function was evaluated by IV ovine Corticotropin Releasing Hormone (o-CRH) administration. We did not find clear-cut abnormalities of NK cytotoxicities either in basal conditions or after exposure to challengers. The extent of cortisol-dependent inhibition was comparable in patients and controls. Significant inverse and direct correlations were found respectively between the spontaneous NK cell activity and baseline serum cortisol at 0800 h (r = -0.5; p < .02), and between IL-2 dependent boosting of NK cell cytotoxicity and ACTH, beta-endorphin or cortisol responses after o-CRH, expressed as areas under the curve (AUC) (r = 0.46, p < .05; r = 0.46, p < .05; and r = -0.48, p < .05, respectively). Correlations observed with AUC ratios yielded more significant results (r = 0.62; p < .01 and r = 0.51; p < .05 respectively). These data suggest a role for Proopiomelanocortin (POMC) derived peptides in the regulation of NK cell activity in AN, and multifaceted relationships between this particular immune function, on the one hand, and certain patterns of HPA axis function on the other.
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PMID:Hypothalamic-pituitary-adrenal axis function, psychopathological traits, and natural killer (NK) cell activity in anorexia nervosa. 948 3

Proopiomelanocortin (POMC) is a precursor polypeptide for various bioactive peptides, including adrenocorticotropic hormone, alpha-, beta-, and gamma-melanotropin, beta-endorphin, and beta-lipotropin. Although the classical source of POMC is the pituitary, various studies indicate the expression of POMC in several nonpituitary tissues. In this study, in situ hybridization with anti-sense cRNA riboprobe was used to show expression of POMC mRNA in human epidermis and cultured human epidermal cells (melanocytes and keratinocytes). POMC mRNA was amplified by reverse transcriptase-polymerase chain reaction using anti-sense and sense primers designed from Exons 2 and 3 of POMC gene. A approximately 300 bp product was present in normal human skin, grafted human skin, and cultured normal human melanocytes and keratinocytes. By Southern analysis this product was hybridized specifically to the POMC cDNA. Sequence analysis of the reverse transcriptase polymerase chain reaction product from tissues or cells showed 85% homology to POMC cDNA from human, bovine, pig, and monkey sources. This suggests the existence of a putative isoform or variant of POMC mRNA in human epidermis.
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PMID:Identification and sequencing of a putative variant of proopiomelanocortin in human epidermis and epidermal cells in culture. 1020 40

Proopiomelanocortin (POMC) is the precursor for a number of biologically active peptides such as adrenocorticotropic hormone (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin. It is well known that these peptides are involved in the stress response in fish as well as in mammals. We have cloned two different carp POMC cDNAs called, POMC-I and POMC-II. The nucleotide sequences of 955 bp for POMC-I and 959 bp for POMC-II share 93.5% identity in their cDNAs, and the deduced amino acid sequences (both 222 amino acids) are 91.4% identical. In the ACTH and beta-MSH domain, two amino acid substitutions are found, whereas alpha-MSH and beta-endorphin are identical. For beta-MSH, the serine replacement (in POMC-I) by a glycine (in POMC-II) results in a putative amidation site Pro-X-Gly for POMC-II. We used RT-PCR to show that both POMC mRNAs are expressed in the hypophysis, hypothalamus and other parts of the brain of a single fish. Furthermore, in a phylogenetic tree based on POMC sequences the divergence of carp POMC-I and -II from tetraploid animals (salmon, trout and xenopus) is demonstrated.
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PMID:Cloning and expression of two proopiomelanocortin mRNAs in the common carp (Cyprinus carpio L.). 980 47

Over the years there has been much debate as to whether alpha-MSH has a role as a pigmentary hormone in humans. There are two main reasons for this. First, despite the observations in the 1960s that alpha-MSH increased skin darkening in humans, there are reports that the peptide has no effect on melanogenesis in cultured human melanocytes. Second, the human pituitary, unlike that of most mammals, secretes very little alpha-MSH and circulatory levels of the peptide in humans are extremely low. However, there is now evidence from several groups that alpha-MSH is capable of stimulating melanogenesis in cultured human melanocytes. Rather than producing an overall increase in melanin production, it appears that the peptide acts specifically to increase the synthesis of eumelanin. Such an action could well explain the previously observed skin darkening effects of alpha-MSH. It is also now known that alpha-MSH is not produced exclusively in the pituitary but has been found at numerous sites, including the skin where it is produced by several cell types. Related Proopiomelanocortin (POMC) peptides such as ACTH are also produced in human skin. The ACTH peptides act at the same receptor (MC-1) as alpha-MSH and certain of these would appear to be more potent than alpha-MSH in stimulating melanogenesis. The ACTH peptides are also present in greater amounts than alpha-MSH in human epidermis and it is likely that they play an important role in regulating pigmentary responses. These POMC peptides are released from keratinocytes in response to ultraviolet radiation (UVR) and it has been proposed that they serve as paracrine factors in mediating UV induced pigmentation. Their production by keratinocytes could therefore be critical in determining pigmentary responses and any changes in the availability of these POMC peptides might explain the variations in tanning ability seen in different individuals. However, the possibility that tanning ability is also dependent upon differences at the level of the MC-1 receptor cannot be ruled out and it has been suggested that an inability to tan may depend upon the presence of non-functional changes at the MC-1 receptor. alpha-MSH does, of course, affect human melanocytes in several ways and its stimulation of melanogenesis could be the consequence of some other fundamental action in the melanocyte. The peptide also has many other target sites in the skin and while it may have a role in regulating skin pigmentation in humans, it should not be viewed solely as a pigmentary peptide. alpha-MSH clearly has many different actions and its primary role in the skin may be to maintain homeostasis.
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PMID:Does alpha-MSH have a role in regulating skin pigmentation in humans? 987 97


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