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)

Proopiomelanocortin and its derivative peptides alpha MSH and beta-endorphin are produced by Leydig cells. beta-Endorphin or another testicular opiate is believed to suppress Sertoli cell hypertrophy. The goal of this study was to determine the effects of another proopiomelanocortin-derived peptide on Sertoli cells. The activities of both alpha MSH and des-acetyl alpha MSH have been compared, since this latter peptide has been identified in testicular extracts. Both alpha MSH and des-acetyl alpha MSH stimulated cAMP accumulation in the media of primary Sertoli cell cultures when incubated in the presence of a phosphodiesterase inhibitor, FSH or forskolin. Both peptides shifted the FSH dose-response curve to the left, making the cells more sensitive to this gonadotropin. The apparent potencies of alpha MSH and its des-acetyl derivative, as measured in Sertoli cells, were similar. We conclude that the MSHs are one of a group of modulators regulating Sertoli cells via the cAMP system, and Sertoli cells are equally responsive to alpha MSH and des-acetyl alpha MSH, unlike central nervous system and melanocytes which show differential responses to these peptides.
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PMID:Stimulation of adenosine 3',5'-monophosphate production in rat Sertoli cells by alpha-melanotropin-stimulating hormone (alpha MSH) and des-acetyl alpha MSH. 241 22

It is generally accepted that human beta-melanocyte-stimulating hormone (h beta MSH) does not normally exist in humans but was merely an artifactually generated 22-amino acid peptide corresponding to a lipotropin (LPH) fragment (residues 35-56). We examined whether the shorter 18-amino acid peptide h beta MSH-(5-22) could be detected in some human tissues. Normal human pituitaries and hypothalami as well as corticotropin-secreting pituitary and nonpituitary tumors were extracted and chromatographed on Sephadex G-50, and the fractions were measured with two radioimmunoassays using either a COOH-terminal human gamma LPH (h gamma LPH) antiserum that recognized equally h gamma LPH, h beta MSH, and h beta MSH-(5-22) or a mid-portion h gamma LPH antiserum that recognized h gamma LPH and h beta MSH but not h beta MSH-(5-22). Normal pituitaries and pituitary tumors contained a single immunoreactive material coeluting with h gamma LPH. The hypothalami and the nonpituitary tumors all contained h gamma LPH and a smaller molecular weight material that was only detected in the COOH-terminal h gamma LPH radioimmunoassay; its elution volume (Ve/V, 0.75) was identical to that of h beta MSH-(5-22) but different from that of h beta MSH (Ve/V, 0.60); on reversed-phase HPLC, it coeluted with synthetic h beta MSH-(5-22) with a retention time different from that of h beta MSH. It is concluded that h beta MSH-(5-22) that corresponds to the 18-amino acid peptide h beta LPH-(39-56), flanked by two pairs of basic amino acids within the h beta LPH molecule, is a normal maturation product of proopiomelanocortin in human nonpituitary tissues.
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PMID:Human beta-melanocyte-stimulating hormone revisited. 243 1

This study evaluates the presence of proopiomelanocortin (POMC)-related peptides in four embryos and eight fetal pituitaries starting from 5 to 25 weeks of pregnancy. Moreover, fetal membranes (amnion and chorion) were also investigated. Freshly collected samples were boiled in acetic acid to destroy enzymes, homogenized and submitted to high performance liquid chromatography (linear gradient from 25 to 40% acetonitrile in 0.01 M HCI, in 15', 1.5 ml/min). The collected fractions were tested for the presence of beta-lipotrophin (beta-LPH), beta-endorphin(beta-EP), gamma-endorphin(gamma-EP) through RIAs. beta-EP and beta-LPH were detected from 7 weeks of pregnancy while gamma-EP appeared later. Only the cephalic portion of the embryos contained the peptides where beta-LPH predominates while no immunoreactivity was detected in the rostral one. In the fetal pituitary there is a progressive increase of gamma-EP according to the gestational age and both beta-EP and beta-LPH showed a trend toward constancy in the 15-25 week range. Amnion and chorion contain a significant amount of the three peptides. Their ontogenesis starts earlier than in the embryo; beta-LPH or beta-EP were detected at 5 weeks of pregnancy. In both tissues beta-EP was higher in the first than in the second trimester. These data demonstrate a different pattern of POMC ontogeny and processing between the conceptus and his environment. This suggests that the POMC-related opiod system of the fetus and of fetal adnexes are independent of each other, possibly subserving to different functions.
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PMID:Proopiomelanocortin-related peptides in feto-placental structures throughout pregnancy. 243 58

The concentration of mRNA encoding proopiomelanocortin (POMC) was measured in AtT-20/D-16v cells, a clonal pituitary tumor cell line. Treatment of the cells with potassium (20 mM) or veratridine (10 microM) for 12, 24 and 48 h caused a time-dependent increase in the levels of POMC mRNA which became significant after 24 h. These effects were not seen in the presence of the sodium channel blocker tetrodotoxin (5 microM). In addition, the calcium channel blocker verapamil (10 microM) completely abolished the responses to either potassium or veratridine, whereas the calcium channel agonist Bay K 8644 (0.1 microM) potentiated the effect of potassium. Furthermore, the calcium channel blockers verapamil (10 microM) and nidefipine (1 microM) significantly decreased not only basal levels of POMC mRNA but also the increase of mRNA levels induced by corticotropin-releasing factor (CRF; 0.1 microM), 8-bromo-cAMP (1 mM) or cholera toxin (100 ng/ml). The drug-induced alterations in the mRNA POMC levels of the cells were, in each case, associated with similar alterations of immunoreactive beta-endorphin in the medium. These results indicate that membrane depolarization to activate sodium channels and calcium channels initiates an entry of calcium ions which triggers POMC gene expression in the AtT-20 cells. Moreover, calcium entry into the cells may exert a tonic stimulatory effect on POMC mRNA under basal conditions and may also contribute to the enhancing effect of CRF or cAMP on POMC mRNA in these cells.
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PMID:Influence of calcium ions on proopiomelanocortin mRNA levels in clonal anterior pituitary cells. 244 1

The influence of adrenalectomy and corticosterone substitution was investigated on Leu-Phe cleaving endopeptidase activity and on the levels of gamma-endorphin and beta-endorphin in the pituitary gland and the brain. The enzyme activity was quantitated by a specific radiometric assay based on the cleavage of the Leu17-Phe18 bond in a NH2- and COOH-terminally protected synthetic substrate which was analogous to beta-endorphin-(15-19). This activity may mimick the formation of gamma-endorphin. beta-Endorphin and gamma-endorphin were measured by specific radioimmunoassays. After 14 days of adrenalectomy enzyme activity had increased in anterior (15%) and neurointermediate lobes of the pituitary gland (30%), hypothalamus (25%), and liver (15%). This increase was prevented when the adrenalectomized animals were subjected to chronic corticosterone substitution by subcutaneous implantation of a pellet of 100 mg. Extirpation of only the adrenal medulla did not affect the Leu-Phe cleaving activity. Enzyme activity in the septum, hippocampus, and cerebellum had not changed after adrenalectomy. Determination of immunoreactive levels of gamma- and beta-endorphins showed that in the anterior pituitary gland gamma- and beta-endorphins had increased by 275 and 300%, respectively, 14 days after adrenalectomy. No significant changes were observed in endorphin levels of the intermediate lobe of the pituitary gland, hypothalamus, hippocampus, and septum. The results indicate that Leu-Phe cleaving endopeptidase activity in sensitive to glucocorticoids in tissues containing proopiomelanocortin-producing cells, i.e., anterior and neurointermediate pituitary gland and the hypothalamus. In the anterior pituitary gland it is correlated with the levels of gamma- and beta-endorphins.
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PMID:Leu-Phe cleaving endopeptidase activity, gamma-endorphin, and beta-endorphin in the rat pituitary gland and brain. Effect of adrenalectomy and corticosterone substitution. 244 2

Opioid peptides have a variety of actions on inter alia pituitary hormone secretion and the immune system. Release of endogenous opioids has been found to stimulate growth of experimental breast cancers and opiate receptor blockers have reduced the growth of chemically induced rat breast tumors. Opioid peptides may therefore play a role in human breast cancer. Invasive ductal carcinomas from 61 premenopausal women were immunocytochemically analyzed for the presence of opioid peptide immunoreactivity. Positive staining was unambiguously identified in 34 of the tumors (56%). In addition, a medullary carcinoma was positive. In a smaller series of tumors, opioid peptide immunoreactive cells were detected in both primary tumors and metastases. Positive tumor cells were usually few and scattered. Therefore, underestimates of their true frequency of occurrence are likely to have occurred, making accurate correlations with clinical behavior and estrogen receptor status difficult. No correlations with estrogen receptors were established for the unambiguously opioid peptide-positive tumors. Many of the positive tumors also stained with antibodies to gamma-endorphin and alpha-melanocyte-stimulating hormone, suggesting the presence of proopiomelanocortin-derived peptides in them. However, peptides derived from other opioid precursors also may be present in breast cancer.
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PMID:Immunoreactive opioid peptides in human breast cancer. 246 45

The present study describes the topography of immunoreactive (ir) oxytocin (OXY) and vasopressin (AVP) neurons in the forebrain of Equus caballus and the coexistence of ir proopiomelanocortin (POMC)-derived peptides in the same cells. These data are compared to those for other mammalian species and the possible significance of species variations is considered. As expected, magnocellular neurons of the equine hypothalamus, which contain ir OXY or AVP, have prominent discernible projections to the neurohypophysis. Further, as in other mammalian species, the field of ir OXY perikarya generally extends rostral and dorsal to groups of ir AVP cell bodies, and caudal projections from OXY neurons appear to be more numerous than ir AVP projections to the brainstem and/or spinal cord. Interestingly, however, the brain of E. caballus also contains: (1) perikarya staining for OXY in the arcuate nucleus, (2) ir AVP and OXY cell bodies in the suprachiasmatic nucleus, and (3) neurons in the supraoptic and paraventricular nuclei that stained for beta-endorphin but not for other posttranslational products of POMC or dynorphin. These results give further credence to the proposal that there is an evolutionary relationship between OXY-, AVP- and POMC-producing hypothalamic neurons. Whether or not species differences in peptide coexistence reflect functional differences in neuronal populations or species differences in residual genomic expression by these neuroendocrine cells warrants further investigation.
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PMID:Topography of oxytocin and vasopressin neurons in the forebrain of Equus caballus: further support of proposed evolutionary relationships for proopiomelanocortin, oxytocin and vasopressin neurons. 252 77

The distribution of proopiomelanocortin (POMC)-immunoreactive neurons was examined in the forebrains of nine sexually mature female pigs by indirect biotin-avidin horseradish peroxidase immunocytochemistry. Primary antiserum against ovine beta-endorphin (Bioflex #BF-EP-3-1) yielded positive staining of neuronal perikarya and processes. Adjacent control sections treated either with primary antiserum preabsorbed with beta-endorphin or substituted with normal rabbit serum lacked specific staining. POMC-immunoreactive cells were located in the anterior and intermediate lobe of the pituitary gland. POMC-immunoreactive perikarya were located in the arcuate nucleus and periarcuate area. The pituitary stalk/median eminence contained sparsely distributed POMC-immunoreactive fibers, which were confined to the zona interna. POMC-immunoreactive fibers were located in the arcuate nucleus and extended rostrally from the arcuate nucleus into the telencephalon coursing adjacent to the wall of the third ventricle as well as through the anterior hypothalamus, suprachiasmatic, supraoptic nuclei and preoptic areas to the nucleus accumbens, diagonal band of Broca, olfactory tubercle, bed nucleus of the stria terminalis and the ventro-lateral aspect of the septum. Caudal projections extended along the wall of the third ventricle to the level of the mammillary bodies and also coursed dorsally, passing through the periventricular, paraventricular, and dorsal medial nuclei of the hypothalamus to the midline thalamic nuclei and habenular nucleus. Lateral projections extended from the arcuate nucleus along the dorsal aspect of the optic tract and terminated in the amygdaloid complex. The distribution of POMC-immunoreactive perikarya and fibers is similar to that of the luteinizing hormone-releasing hormone (LHRH) fiber network. Therefore the opportunities exist, anatomically, for interactions between the POMC and the LHRH systems.
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PMID:Localization of proopiomelanocortin (POMC) immunoreactive neurons in the forebrain of the pig. 252 70

We investigated regulation of the dynamic state of enkephalin and endorphin brain stores during morphine tolerance and dependence using cDNA hybridization and radioimmunoassay of the biologically active peptide(s) and their respective peptide precursors. Rats were made tolerant to morphine with the subcutaneous implantation of three morphine pellets (75 mg each) for a period of five days. Hypothalamic proopiomelanocortin (POMC) mRNA, POMC, and corticotropin-like intermediate lobe peptide content were decreased by 50% in morphine-dependent rats. However, beta-endorphin content remained unchanged. Enkephalin and proenkephalin mRNA content in various brain structures failed to change. A single injection of naltrexone (2 mg/kg) 1 hour before decapitation did not reverse the decrease in POMC mRNA and POMC content elicited by morphine. However, a slower, spontaneous withdrawal caused by removal of the pellets did reverse (after two days) the down-regulation of the hypothalamic POMC system. A single injection of morphine (10 mg/kg) failed to affect any parameter used to assess the dynamic state of opioid peptides.
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PMID:Down-regulation of proopiomelanocortin synthesis and beta-endorphin utilization in hypothalamus of morphine-tolerant rats. 253 67

Peptides derived from proopiomelanocortin (POMC) have been found to stimulate the proliferation of murine myogenic cells. Among these peptides, adrenocorticotropin (ACTH) and alpha-, beta-, and gamma-melanocyte-stimulating hormones (MSH) were found to be active, whereas the opioid peptides were not. At clonal density, both ACTH and MSH caused a three- to fourfold increase in the average number of cells per clone in myogenic but not in fibroblast colonies. At high cell density, ACTH and MSH caused a three- to fourfold increase in proliferation of myogenic cells, reflected by an increased accumulation of skeletal myosin. On the other hand mouse embryo skin or muscle fibroblasts or vertebral chondroblasts did not increase proliferation in response to POMC-derived peptides. The half-maximal dose at which ACTH stimulated myoblast proliferation was around 5 nM, and the mitogenic effect was doubled by suboptimal doses of fibroblast growth factor. The possible physiological significance of the mitogenic effect of ACTH on myogenic cells is discussed.
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PMID:Adrenocorticotropin is a specific mitogen for mammalian myogenic cells. 253 37


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