Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinically nonfunctioning pituitary adenomas represent one-third of pituitary tumours submitted to surgery. Symptoms consist mainly of visual impairment and there is no evidence of hormonal hypersecretion. Most nonfunctioning pituitary adenomas express genes of glycoprotein hormone subunit(s), and release these hormones in vitro. Thirty per cent of tumours do not synthesize any recognizable pituitary hormones. The first-line treatment is surgery, with the aim of removing as much of the tumour as possible and of reducing visual defects without excessive risks 80% of patients show visual improvement postoperatively. Tumour remnants exist in 30 to 50% of cases; radiation therapy is applied when tumour removal is incomplete. Recurrence of tumour and visual signs and/or an increase in the size of the tumour is noted in about 20% of cases even after radiation therapy. Medical treatment is used when tumour resection is impossible or hazardous. Long-term dopamine agonist treatment in a few cases can induce rapid and partial improvement and small decrease in tumour size in about 15%. Somatostatin analogues can induce an early visual improvement in limited cases, but little visible tumour shrinkage. GnRH analogues have been used in gonadotrophin-secreting tumours; super agonists seem unable to reduce secretion and tumour size.
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PMID:Management of nonfunctioning pituitary adenomas. 810 55

A 48-year-old man with visual disturbances and subtle features of acromegaly had elevated serum thyrotropin (thyroid-stimulating hormone) levels but was clinically euthyroid and initially had normal blood growth hormone (GH) levels. A computed tomographic scan documented a large pituitary tumor; he underwent incomplete transsphenoidal adenomectomy. Postoperative octreotide treatment failed to shrink the tumor. Rising GH levels necessitated repeated transsphenoidal and, subsequently, frontotemporal resection. By histology, the tumor was a chromophobic adenoma. In the first specimen, immunocytochemistry localized GH, beta-thyrotropin, and alpha-subunit of glycoprotein hormones in adenoma cells. The second specimen also contained prolactin, whereas the third contained only GH and beta-thyrotropin. By electron microscopy, the tumor was bimorphous, composed of elongated thyrotrophs and densely granulated somatotrophs. In tissue culture, the first specimen released GH, thyrotropin, and alpha-subunit and smaller quantities of prolactin; the second specimen released only GH and alpha-subunit; and the third released GH, thyrotropin, alpha-subunit, and prolactin. Incubation with somatorelin (GH-releasing hormone) variably stimulated release of all four hormones in the first and third specimens; protirelin (thyrotropin-releasing hormone) had no effect. Somatostatin consistently inhibited release of all four hormones; inhibition by bromocriptine mesylate was variable. The mild degree of clinical and biochemical acromegaly is unusual for a large macroadenoma, and the reasons for the absence of hyperthyroidism are unclear. These discrepancies may be attributed to retarded hormone release and/or synthesis due to suppression by somatostatin in vivo.
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PMID:Recurrent plurihormonal bimorphous pituitary adenoma producing growth hormone, thyrotropin, and prolactin. 828 35

We report the histological, immunohistochemical and ultrastructural changes in mice containing a chimeric glucagon-simian virus 40 T antigen (SV40Tag) gene. Transgene expression was detected in endocrine cells of pancreas, small and large intestine. Hyperplasia of glucagon-containing cells developed in pancreas and large bowel by gestational day 19. In large bowel, hyperplastic cells increased in number postnatally and invasive carcinomas were identified at 4 weeks; several animals had lymph node metastases. In contrast, no pathology was detected in the small bowel in any of the transgenic mice. Colonic tumours expressed SV40Tag, proglucagon-derived peptides and peptide YY (PYY); scattered cells contained cholecystokinin or glycoprotein hormone alpha-subunit. Somatostatin or serotonin was also detected in some tumours. By electron microscopy, the colonic tumours retained features of endocrine differentiation, but secretory granules were smaller than those of non-tumorous intestinal glucagon-producing L cells. In postnatal pancreas, atypical cells containing SV40Tag and glucagon were initially clustered at the periphery of islets; this atypical hyperplasia progressed to neoplasia by 11-12 weeks. Some neoplastic pancreatic cells contained glucagon, PYY or vasoactive intestinal peptide immunopositivity, but most were negative for all peptides; they contained immunoreactivity for tyrosine hydroxylase and by electron microscopy, pancreatic tumour cells had neuronal features. Pancreatic polypeptide was not detected in the non-tumorous islets of transgenic animals. This line of transgenic mice provides a model for the analysis of endocrine tumour progression in the gut and pancreas.
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PMID:Development of colonic and pancreatic endocrine tumours in mice expressing a glucagon-SV40 T antigen transgene. 860 71

Neuroendocrine gut and pancreatic tumours have provided a diagnostic and therapeutic challenge over the years. These rather slowly growing neoplasms have been assigned a good prognosis but when liver metastases are present the prognosis is not better than that of most other malignant tumours. Despite the development of improved diagnostic procedures many patients are still referred at a stage of the disease too late for surgical cure, at which time medical treatment is warranted. The diagnosis is based on histopathological diagnosis including silver stainings (Grimelius, Masson) and immunohistochemistry for chromogranin A and synaptophysin. Analysis of chromogranin A in the plasma is an important adjunct in the screening for various types of neuroendocrine gut and pancreatic tumours. About 80%-100% of patients with verified neuroendocrine gastrointestinal tumours have elevated circulating levels of this glycoprotein. Depending on clinical symptoms the chromogranin A analysis is supplemented by other peptide hormone analyses as well as urinary 5-HIAA for patients with midgut carcinoid tumours. In the past the localization procedures were based on CT, MRI and ultrasound investigations but in recent years somatostatin receptor scintigraphy (octreoscan) and endoscopic ultrasonography have significantly improved the diagnostic potential. Almost 80% of neuroendocrine gastrointestinal tumours present somatostatin receptor subtype 2 binding 111Indium-labelled octreotide which can be used for staging of the disease, and which also indicates whether or not somatostatin analogues can be used in the treatment of these tumours. Surgery is still a cornerstone in the treatment of neuroendocrine gastrointestinal tumours, even if the patients are beyond cure. Debulking procedures and bypassing operations are important for improving clinical condition and facilitating impending medical treatment, and during the past decade a more aggressive surgical approach has emerged. The medical treatment is based on chemotherapy, and the use of somatostatin analogues and alpha-interferons. Chemotherapy, in particular the combination of streptozotocin with 5-FU or doxorubicin, is still first-line treatment for most endocrine pancreatic tumours, while somatostatin analogues and alpha-interferons are considered first-line for classical midgut carcinoids. Chemotherapy and biotherapy can be combined in many patients, and changes from one medical treatment to another during the course of the disease is mandatory for control of the disease. It is important to realise that most patients with malignant tumours are not cured by medical treatment but that the disease can be controlled for extended periods of time. In the future it will be possible to individualize treatments on the basis of new information about such features of tumour biology as proliferation capacity, expression of adhesion molecules, and growth factors and their receptors.
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PMID:Neuroendocrine gastrointestinal tumours. 883 99

Fetal antigen 1 (FA1) is a glycoprotein containing six epidermal growth factor (EGF)-like repeats. It is closely similar to the protein translated from the human delta-like (dlk) cDNA and probably constitutes a proteolytically processed form of dlk. dlk is homologous to the Drosophila homeotic proteins delta and notch and to the murine preadipocyte differentiation factor Pref-1. These proteins participate in determining cell fate choices during differentiation. We now report that FA1 immunoreactivity is present in a number of neuroectodermally derived tumours as well as in pancreatic endocrine tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing development, gradually disappeared from these cells and became restricted to insulin-producing beta cells. Throughout development FA1 was not detected in endocrine glucagon, somatostatin or pancreatic polypeptide cells. Moreover, developing insulin cells that coexpressed glucagon were negative for FA1. Thus, there was a negative correlation between FA1 and glucagon both in tumours and during development. These results, together with FA1/dlk's similarity with homeotic proteins, point to a role of FA1 in islet cell differentiation.
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PMID:FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression. 898 41

In this study, we have found that IGF-binding protein-3 (IGFBP-3) in calf serum added to tissue culture medium is degraded by cultured FRTL-5 cells and a major 31 kDa fragment of IGFBP-3 is produced. When FRTL-5 rat thyroid cells were cultured in 6H medium (modified F-12M medium containing TSH, insulin, hydrocortisone, somatostatin, transferrin, and glycyl-histidyl-lysine) containing 5% calf serum, both 44-46 and 31 kDa IGFBPs were found in conditioned medium by ligand blot analysis using 125I-labelled IGF-II. However, predominantly the 44-46 kDa IGFBP was detected in unconditioned 6H medium containing 5% calf serum. When calf serum in the media was replaced by human serum similar results were obtained, and the 44-46 kDa and 31 kDa IGFBPs were recognized using a human IGFBP-3 antibody following Western blot analysis. FRTL-5 cells secreted only small amounts of an endogenous 29 kDa IGFBP, thought to be IGFBP-5. To separate the 31 kDa fragment of IGFBP-3 from the endogenous IGFBP-5, culture media were fractionated by concanavalin-A-Sepharose chromatography and aliquots of both flow-through and eluate from the column were analyzed by ligand blotting. A 31 kDa IGFBP was found in the eluate fractions from concanavalin-A-Sepharose chromatography following the separation of conditioned 6H medium supplemented with calf serum, suggesting that this species was an N-linked glycoprotein and could be derived from the degradation of serum IGFBP-3 by FRTL-5 cells. Using a modified zymographic assay, we examined whether the degradation of IGFBP-3 could depend on the cell membrane. Confluent FRTL-5 cells were washed with PBS and overlaid with liquid agarose solution. After the agarose had solidified, unconditioned 6H medium containing 5% calf serum was incubated with the cells at 37 degrees C for 16 h. Both 44-46 and 31 kDa IGFBP species were found in the overlying, conditioned medium by ligand blot. However, the 31 kDa IGFBP was not found in medium in the absence of FRTL-5 cells, and no IGFBP could be found in serum-free conditioned medium from agarose-covered FRTL-5 cells. This suggests that the 44-46 kDa IGFBP-3 in serum was degraded to yield a 31 kDa fragment, while any endogenous IGFBP-5 could not pass out of the agarose. The degradation of 44-46 kDa IGFBP-3 in the modified zymographic assay was inhibited by phenylmethylsulfonyl fluoride, EDTA, and aprotinin, but not by leupeptin. In summary, these results indicated that IGFBP-3 in calf serum added to culture medium could be degraded by FRTL-5 cells and that this may involve calcium-dependent serine proteases.
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PMID:Degradation of IGF-binding protein-3 by proteases in cultured FRTL-5 rat thyroid cells. 907 84

G-protein-coupled or 7-transmembrane receptors (7TMRs) are often studied after heterologous expression in mammalian cells such as COS-7, CHO-K1, or HEK-293s. In this paper, we describe the development of a rapid and generic method for producing stable Chinese hamster ovary cell lines expressing high levels of recombinant 7TMRs by N-terminal tagging these proteins with the hemagglutinin (HA) sequence. To illustrate the broad applicability of this technique, we have presented data from cell lines expressing a glycoprotein hormone receptor for follicle-stimulating hormone (FSHR), CXC- (CXCR-2), and CC-chemokine (CCR-1) receptors and peptide receptors from the somatostatin (SSTR1, 2, 5) and neuropeptide Y (NPY-Y2, -Y4 Rs) families. Typically, cell lines with a receptor density of 1 to 15 pmol/mg protein are produced with this method. The presence of the HA tag does not adversely affect the binding or functional activity of the receptors.
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PMID:A generic method for the production of cell lines expressing high levels of 7-transmembrane receptors. 923 98

To observe the distribution of multiple hormones in nonsecreting islet cell tumors of the pancreas and to study their histogenesis, 9 pancreas nonsecreting islet cell tumor cases were studies using 12 kinds of antisera. The results showed that 4 cases were positive for insulin, 6 for glucagon, 1 for gastrin, 6 for somatostatin, 1 for gastrin 5 for calcitonin, 7 for neurotensin, 4 for ACTH, 3 for TSH, 5 for FSH and 2 for LH. It is therefore confirmed that these tumors synthesize and secrete peptide hormones and glycoprotein hormones. We believe that these endocrine cells originate from primitive multipotential stem cells.
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PMID:[Immunohistochemical studies of nonsecreting pancreatic islet cell tumors secreting many hormones]. 938 78

The ability of T cells to adhere to and interact with components of the blood vessel walls and the extracellular matrix is essential for their extravasation and migration into inflamed sites. We have found that the beta1 integrin-mediated adhesion of resting human T cells to fibronectin, a major glycoprotein component of the extracellular matrix, is induced by physiologic concentrations of three neuropeptides: calcitonin gene-related protein (CGRP), neuropeptide Y, and somatostatin; each acts via its own specific receptor on the T cell membrane. In contrast, substance P (SP), which coexists with CGRP in the majority of peripheral endings of sensory nerves, including those innervating the lymphoid organs, blocks T cell adhesion to fibronectin when induced by CGRP, neuropeptide Y, somatostatin, macrophage inflammatory protein-1beta, and PMA. Inhibition of T cell adhesion was obtained both by the intact SP peptide and by its 1-4 N-terminal and its 4-11, 5-11, and 6-11 C-terminal fragments, used at similar nanomolar concentrations. The inhibitory effects of the parent SP peptide and its fragments were abrogated by an SP NK-1 receptor antagonist, suggesting they all act through the same SP NK-1 receptor. These findings suggest that neuropeptides, by activating their specific T cell-expressed receptors, can provide the T cells with both positive (proadhesive) and negative (antiadhesive) signals and thereby regulate their function. Thus, neuropeptides may influence diverse physiologic processes involving integrins, including leukocyte-mediated migration and inflammation.
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PMID:Neuropeptides, via specific receptors, regulate T cell adhesion to fibronectin. 955 39

A pituitary glycoprotein hormone FSH stimulates ovarian granulosa cells to induce ovarian follicular development. In this study we identified rat ovarian genes that were rapidly induced by FSH in the cultured rat granulosa cells by means of subtraction cloning. Complementary DNA clones encoding cAMP responsive element binding modulator (CREM) were identified as one of the FSH inducible genes. Northern blotting and reverse transcription and polymerase chain reaction (RT-PCR) analyses revealed that only the repressor type of CREM gene products, ICER (inducible cAMP early repressor) isoforms, were induced by FSH treatment in cultured rat granulosa cells. The induction of ICER by FSH was mimicked by reagents known to increase intracellular cAMP levels, indicating that the induction is through cAMP and protein kinase A signal transduction system. Induction of ICER was also confirmed as the protein levels. Electrophoretic mobility shift assay of granulosa cell extracts with a radiolabeled double stranded oligonucleotide corresponding to somatostatin cAMP responsive element also revealed that only the ICER proteins were induced by FSH treatment, whereas levels of CREM proteins were nearly constant regardless of the FSH treatment. Our present study demonstrates that FSH-induced and cAMP-mediated induction and attenuation of transcriptional responses by CREM gene products may be a key mechanistic component for the granulosa cell differentiation and proliferation.
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PMID:Regulation of cAMP responsive element binding modulator isoforms in cultured rat ovarian granulosa cells. 1020 56


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