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 (POMC), a precursor protein for ACTH, beta-endorphin, and the MSHs, has been identified in the reproductive tracts of both male and female. With rat pituitary POMC complementary DNA (cDNA) as a hybridization probe, POMC-like messenger RNA (mRNA) was identified in the ovaries of rat, mouse, and monkey. The molecular size of POMC-like mRNA in the ovary was 150-200 bases smaller than in the pituitary and hypothalamus but identical to that in the testis and epididymis. The size heterogeneity of POMC mRNA observed in various tissues is not due to differences in the lengths of the poly(A) tail, as measured by RNase H digestion. S1 nuclease mapping analysis revealed that POMC mRNAs isolated from pituitary, testis, or ovary share the nucleotide sequences coding for ACTH, beta-lipotropin, and the 3'-untranslated region. The regulation of ovarian POMC-like mRNA was also investigated. Treatment of 25-day-old immature female rats with PMSG resulted in profound increases in the ovarian content of total RNA, poly(A) RNA, and POMC-like mRNA. The concentration of ovarian POMC-like mRNA during pregnancy increased increased to 3-4 times that in immature or normally cycling animals. POMC-derived peptides are present in the human placenta and are synthesized de novo in cultured placental cells. In this report we also demonstrate POMC-like mRNA in the placenta of rat, mouse, and human. The size of POMC-like mRNA in the placenta was similar to that observed in the testis, epididymis, and ovary and different from that found in the pituitary or hypothalamus. The concentration of placental POMC-like mRNA did not change throughout pregnancy. In conclusion, we have demonstrated that 1) POMC-like mRNA is present in the ovary and placenta of rodents and primates; 2) the size of POMC-like mRNA in the ovary and placenta, like that in the testis and epididymis, is smaller than that in the pituitary and hypothalamus, probably owing to a shortening of the 5'-ends; and 3) the expression of this gene is regulated by gonadotropins in the ovary but probably not in the placenta.
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PMID:Expression and regulation of proopiomelanocortin-like gene in the ovary and placenta: comparison with the testis. 242 19

We have previously demonstrated low levels of immunoreactive (ir)-beta-endorphin (beta-EP) and ir-ACTH in a subpopulation of mouse spleen macrophages, which is consistent with an involvement of opioid peptides in modulation of immune responses. Gel chromatography studies suggested the presence of an approximately 3.5,000-molecular weight (mol wt) species, putatively beta-EP, an approximately 11.5,000-mol-wt species, putatively beta-lipotropin, and a higher molecular weight species (putative beta-EP precursor, pro-opiomelanocortin (POMC). In this study we have extended our original findings by demonstrating the presence of messenger RNA for POMC by the use of a complementary DNA probe and Northern blot analysis of extracts of mouse and rat spleen. In addition, using high performance liquid chromatography (HPLC), we have shown that the major endorphin species in mouse spleen macrophages is beta-EP1-31, and that there are smaller amounts of each of the acetylated forms, N-acetyl-beta-EP1-16 (alpha-endorphin), N-acetyl-beta-EP1-17 (gamma-endorphin), N-acetyl-beta-EP1-27, and N-acetyl-beta-EP1-31. We interpret these studies as showing that (a) the spleen is an organ of POMC synthesis and that (b) the predominant COOH-terminal product of macrophage POMC is the opiate-receptor active species beta-EP1-31.
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PMID:Pro-opiomelanocortin messenger ribonucleic acid and posttranslational processing of beta endorphin in spleen macrophages. 242 57

To understand the hormonal regulation of steady-state growth hormone (GH) mRNA levels, we investigated the interaction between somatostatin and agents known to increase intracellular cAMP activity on GH mRNA, GH synthesis, cell content of GH, and GH release in primary cultures of rat anterior pituitary cells. We simultaneously studied the modulation of the steady-state of pro-opiomelanocortin (POMC) mRNA levels by cAMP. In four independent experiments, a 48-hr exposure to 0.3 mM 3-isobutyl-1-methylxanthine (IBMX) or 3 mM 8-bromoadenosine 3',5'-cyclic monophosphate (8Br-cAMP) increased GH mRNA levels from 70 to 170% and from 70 to 150% above control (p less than 0.001), respectively. Parallel increases in GH release accompanied by a corresponding decrease in the intracellular content of GH were also obtained. Following a 48-hr incubation with 100 nM somatostatin alone, no change in GH mRNA levels was observed whereas GH release was inhibited by 90%, GH cell content doubled, and GH synthesis decreased by 40%. Surprisingly, somatostatin potentiated the enhancing effect of 8Br-cAMP on GH mRNA levels. In the same cell preparation, a 48-hr exposure to IBMX or 8Br-cAMP stimulated adrenocorticotropin release by 9.4- and 18.0-fold, respectively, and increased POMC mRNA levels by 2.4- and 2.3-fold (p less than 0.001), respectively. No change in beta-actin mRNA was observed after these treatments. These data indicate that increased intracellular cAMP concentrations increase the steady-state level of GH mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
DNA 1986 Aug
PMID:Regulation of growth hormone mRNA and pro-opiomelanocortin mRNA levels by cyclic AMP in rat anterior pituitary cells in culture. 242 92

Interleukin 2 (IL-2) stimulated the differentiation of human peripheral blood leukocytes into lymphokine-activated killer cells, as well as DNA synthesis of human T lymphocytes. Both effects of IL-2 could be inhibited by prostaglandin E2, a potent stimulator of adenylate cyclase; however, the inhibitory effect of prostaglandin E2 could be overcome by increased concentrations of IL-2. The opposite effects of IL-2 and prostaglandin E2 were paralleled by their respective abilities to inhibit and stimulate cAMP production in intact cells. Other agents, which inhibit adenylate cyclase directly (somatostatin, beta-endorphin, UK 14.3041) or indirectly by activation of protein kinase C (phenylephrine), could stimulate both differentiation and proliferation. None of these agents alone or in combination were as effective as maximal concentrations of IL-2. However, all agents potentiated differentiation and proliferation induced by submaximal and maximal concentrations of IL-2. Additionally, combinations of agents which stimulated protein kinase C with those that inhibited adenylate cyclase were additive in the potentiation of IL-2-induced differentiation. Neither inhibition nor potentiation of IL-2-induced lymphokine-activated killer cell differentiation was accompanied by changes in Tac expression or gamma-interferon production. The data indicate that the stimulation of lymphokine-activated killer cell differentiation and lymphocyte proliferation in human cells share a common initial biochemical signal. Although the inhibition of adenylate cyclase is not sufficient to maximally stimulate either process and cannot bypass the requirement for IL-2, modulation of this enzyme complex, positively or negatively, can regulate the ultimate physiologic response to IL-2.
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PMID:Potentiation of lymphokine-activated killer cell differentiation and lymphocyte proliferation by stimulation of protein kinase C or inhibition of adenylate cyclase. 244 68

Patients with medullary thyroid carcinomas (MTC) were analyzed according to age, sex, and tumor stage. In addition, the MTC were screened for the predominant histologic pattern, immunocytochemical spectrum (60 tumors), and DNA content (DNA cytophotometry and DNA flow cytometry, 25 tumors). These findings were correlated with follow-up data available for 45 of these patients. Forty-eight percent of the tumors revealed a polygonal cell pattern, whereas 22% showed spindle-cell predominance. All tumors contained cytokeratin, chromogranin A, and calcitonin (CT). Calcitonin gene-related peptide (CGRP) was present in 92%, carcinoembryonic antigen (CEA) in 77%, neuron-specific enolase (NSE) in 75%, and vimentin in 53% of cases. Positivity for neurotensin, somatostatin, neurofilaments, bombesin, and alpha human chorionic gonadotropin (a-hCG) and serotonin ranged between 3% and 27%. All MTC were negative for substance P, adrenocorticotropic hormone (ACTH), thyroglobulin (TG), or S-100 protein. Local recurrences and regional lymph node metastases revealed identical staining patterns as the primaries. Prognosis of MTC was found not to be related to histologic features (dominant architectural pattern, cellular shape, presence of amyloid deposits) or immunocytochemical pattern. Instead, survival was significantly correlated to age, sex, and stage of disease. The best prognosis was seen in women younger than 40 years and revealing an early stage of disease. DNA measurements added valuable information in assessing the prognosis of MTC.
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PMID:Prognostic factors in medullary thyroid carcinomas. Survival in relation to age, sex, stage, histology, immunocytochemistry, and DNA content. 244 25

Current understanding of the phenomenon of ectopic hormone production is largely based on a histopathological and immunocytochemical analysis of peptide hormone secreting tumours arising in non-endocrine tissues. Recent advances in the study of gene regulation show that the tissue-specific expression of genes is a highly sophisticated process and is unlikely to be disturbed by a spontaneous event such as point mutation in DNA. Study of several genes for frequently found ectopic hormones, i.e. prop-opiomelanocortin, vasopressin/neurophysin II, gastrin-releasing peptide, parathyroid hormone-related peptide, calcitonin gene-related peptide and beta-chorionic gonadotropin, suggests they are transcribed as they would be in their natural cell of origin. It is argued therefore that these data are compatible with the concept that the tumour cell of origin was capable of expressing these peptides, if only in a minor or transient manner. In one example, the ectopic ACTH syndrome, it is also necessary to explain the non-suppression of this gene's expression by elevated levels of glucocorticoids. Recent work suggests that this may result from physically present, but biologically inactive glucocorticoid receptors, a phenomenon that has occasionally been noted in hormonally inactive tumour tissue and cell lines.
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PMID:Ectopic hormone production. 247 14

1. The effects of 72 h subcutaneous infusion of graded doses of rat CRF and ACTH(1-24) were studied in rats of initial weight 150-170 g. Rat CRF was infused at 30, 100 or 300 ng/h, and ACTH(1-24) at 125, 250 or 500 ng/h. 2. There was a progressive though modest increase in adrenal weight for all CRF doses, and an associated reduction of thymus weight. Circulating ir-ACTH, ir-beta-endorphin and corticosterone levels, and adrenal DNA content, were not increased after 3 days. Adrenal RNA and protein content were increased at the highest CRF dose used. 3. ACTH infusion caused a progressive increase in adrenal weight and thymic involution which was marked at the higher doses; circulating corticosterone levels were not significantly altered by the lowest dose but were significantly raised by the higher doses. As expected, plasma ir-beta-endorphin was suppressed to low levels with all doses. Adrenal DNA did not alter but there were progressive increases in adrenal protein and RNA. 4. There was a marked difference in gain between the two infusion regimens in terms of all parameters measured, suggesting that potent mechanisms exist to temper the pituitary-adrenal response to markedly different levels of peripheral CRF input. The damped effect of CRF infusion compared with that of ACTH may represent desensitization of CRF receptors at the pituitary; alternatively, it may reflect binding and substantial inactivation of CRF in peripheral blood.
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PMID:Effect of 3 day infusion of ACTH or CRF on the pituitary-adrenal axis. 248 98

The endocrine, paracrine, and neurocrine influences of the non-glucose insulin secretion regulators on the pancreatic islets are analysed. Experiments on rats using the primary monolayer culture of isolated islet cells proved that insulin secretion is directly modulated by the growth hormone (GH), C-terminal tetrapeptide of cholecystokinin, thyroliberin, and met-enkephalin, and by certain blood plasma factors of diabetes I patients. In addition, GH is showed to stimulate the islet cell proliferation by intensifying 3H-thymidine incorporation into DNA synthesis. The blood plasma factors of IdDM patients influence the islets of Langerhans activity by either stimulating or depressing the secretory function of insulin producing cells. The aspects of functional organization of the islet cells and complex regulation of insulin secretion are discussed.
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PMID:[Mechanisms of the regulation of insulin secretion]. 250 84

Direct inhibitory effects of neuroendocrine hormones on human ovarian cancer cell proliferation in vitro were examined. Except for melatonin, all neuroendocrine hormones used in this study inhibited proliferation of KF cells derived from human serous cystadenocarcinoma of the ovary in a dose-dependent manner. The degree of inhibition of prostaglandin D2 was most marked being comparable to that of 5-fluorouracil and followed by beta-endorphin, alpha-endorphin, and Met-enkephalin. More than 200 microM melatonin stimulated the cell proliferation. The inhibitory effects by endorphins were partially reversible by 20 microM naloxone. From analyses of uptakes of radiolabeled precursors by the KF cell, endorphins were considered to inhibit protein and RNA syntheses but not DNA synthesis. These results suggest that neuroendocrine hormones may play an important role in regulation of tumor growth.
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PMID:Inhibition of human ovarian cancer cell proliferation in vitro by neuroendocrine hormones. 252 Dec 12

Using Northern blotting with a human genomic DNA probe for the pro-opiomelanocortin (POMC) gene, we have shown specific mRNA in normal human peripheral mononuclear cells (PBMC); the presence of specific mRNA was also observed in a T lymphocyte cell line derived from a patient with lymphoma. We then demonstrated that PBMC translate the message into protein. Thus, using a radioimmunoassay with an antibody for ACTH, a median of 29 pg of ACTH-like immunoreactivity (ACTH-LIR) was found in 10(7) PBMC. ACTH-LIR was also detected in seven different cell lines derived from patients with lymphoid and myeloid malignancies, two of them JM and U937 showing the highest values 135 and 108 pg/10(7) cells, respectively. The chromatographic characterization of this ACTH-LIR showed, at least, three molecular forms of immunoreactive ACTH with molecular weights of the order of 31,000 POMC, 22,000 ACTH, and 4,500 ACTH, in addition to high-molecular-weight material (greater than 43,000). We conclude that PBMC produce ACTH-LIR which may act as a paracrine immunomodulator in a similar way to lymphokines and/or may signal the adrenal gland to secrete glucocorticoids.
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PMID:Expression of pro-opiomelanocortin gene and quantification of adrenocorticotropic hormone-like immunoreactivity in human normal peripheral mononuclear cells and lymphoid and myeloid malignancies. 253 7


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