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)

The effect of somatostatin on the secretion of calcitonin was studied in four patients with medullary carcinoma of the thyroid (MCT). The basal serum calcitonin level was markedly elevated in all cases. A bolus injection (100 microgram) of somatostatin followed by an intravenous infusion (5 microgram/min) for 60 min suppressed the basal calcitonin level in three of the four patients by 24-42%, while it had no inhibitory effect in one case. In another experiment, the pentagastrin-stimulated (6 microgram/kg s.c.) calcitonin release was partially blocked by a simultaneous i.v. injection of somatostatin (200 microgram) in all four patients studied. These experiments add human calcitonin to the list of hormones whose release in inhibited by somatostatin.
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PMID:Somatostatin inhibits the pentagastrin-induced release of serum calcitonin in medullary carcinoma of the thyroid. 64 84

Somatostatin has recently been applied therapeutically for hypercalcitonemia in patients with calcitonin-producing tumours. Using calcitonin-secreting cells (C-cells) of the medullary thyroid carcinoma cell line rMTC 44-2, we investigated the inhibitory action of somatostatin on calcitonin release, cytosolic Ca2+ and Ca2+ channel currents. The Ca(2+)-induced rises of the cytosolic Ca2+ and calcitonin secretion were greatly inhibited by somatostatin or its stable analogue octreotide. The effects of somatostatin were pertussis toxin-sensitive. Under voltage clamp conditions, C-cells exhibited slowly inactivating Ca2+ channel currents. Bath application of 100 nM somatostatin reversibly reduced the Ca2+ channel current by about 30%. The Ca2+ channel current and its inhibition by somatostatin were not affected by intracellularly applied cyclic AMP. Moreover, pretreating the cells with pertussis toxin had no effect on the control Ca2+ channel currents but greatly abolished its inhibition by somatostatin. The data show that somatostatin suppresses the Ca(2+)-stimulated calcitonin secretion by inhibiting voltage-dependent Ca2+ channel currents and by lowering cytosolic Ca2+. These actions of somatostatin involve pertussis toxin-sensitive G-proteins and occur independently of changes in the cyclic AMP concentration.
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PMID:Inhibition of Ca(2+)-induced calcitonin secretion by somatostatin: roles of voltage dependent Ca2+ channels and G-proteins. 134 29

The transactivation of genes through the cAMP-regulated enhancer (CRE) is proposed to occur by the binding and phosphorylation of the transcription factor CREB (CRE-binding protein). Originally believed to be a single protein, more than 10 different CREB proteins have been cloned. The contributions of each of these factors to gene regulation have yet to be determined unambiguously. We have isolated a CREB cDNA that contains a mutation of a single amino acid in the DNA-binding domain. In gel shift assays, this mutant, designated KCREB, is unable to bind to the somatostatin (SS) CRE. In addition, KCREB acts as a dominant repressor of the wild-type factor, blocking the ability of wild-type CREB to bind to the CRE when present as a KCREB:CREB heterodimer. The KCREB mutant also acts as a dominant repressor in vivo, completely blocking the ability of wild-type CREB to mediate induction by protein kinase-A of a SS CRE reporter gene in F9 teratocarcinoma cells. We have used this mutant to analyze the participation of CREB in the induction of the SS promoter in CA-77 cells, a medullary thyroid carcinoma cell line that produces high levels of SS. Although KCREB can block a portion of the cAMP induction of the SS promoter in CA-77 cells, approximately 45% of the induction remains insensitive to the mutant. These data support the paradigm that CREB is involved in the cAMP induction of SS in vivo. Furthermore, the inability of KCREB to completely block cAMP-mediated SS expression in CA-77 cells suggests that additional factors may contribute to the cAMP regulation of CRE function.
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PMID:A dominant repressor of cyclic adenosine 3',5'-monophosphate (cAMP)-regulated enhancer-binding protein activity inhibits the cAMP-mediated induction of the somatostatin promoter in vivo. 135 57

The effect of somatostatin on cAMP accumulation and calcitonin secretion in C-cells of the rat medullary thyroid carcinoma cell line rMTC 6-23 was investigated. Intracellular cAMP accumulation as well as calcitonin secretion could be dose-dependently stimulated by rat growth hormone releasing factor (rGRF). The long-acting somatostatin analogue octreotide inhibited rGRF-stimulated cAMP accumulation and calcitonin secretion dose dependently but failed to block 8-bromo-cAMP-stimulated calcitonin secretion. The inhibitory effect of octreotide on rGRF-induced calcitonin secretion was partially abolished by pretreating the cells with pertussis toxin. The octreotide effect was not due to changes in the degradation of cAMP, as it was similarly seen in the presence of isobutylmethylxanthine. Thus we conclude that pertussis toxin-sensitive G-proteins are involved in the cAMP-mediated regulation of calcitonin secretion in C-cells.
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PMID:Inhibitory effect of somatostatin on cAMP accumulation and calcitonin secretion in C-cells: involvement of pertussis toxin-sensitive G-proteins. 135 52

The recent availability of the long-acting somatostatin analogue, octreotide, has allowed its therapeutical use in a wide variety of human diseases, including some digestive, neoplastic and autoimmune disorders. This review focuses on the treatment of some endocrine disorders with octreotide. Evidence is accumulating that octreotide treatment is effective in improving the cure rate of pituitary surgery in acromegaly by shrinking the tumour size, and in lowering GH and IGF-I levels in the vaste majority of patients. Octreotide is also effective in ameliorating TSH-induced hyperthyroidism in patients with TSH-secreting adenomas. Moreover, octreotide has proved useful in the management of endocrine tumours of the gastroenteropancreatic tract (vipomas, glucagonomas, gastrinomas, insulinomas, and carcinoids) by reducing hormone levels and in some instances the size of the primary and/or metastatic lesions. Besides the above well-established indications there are some other potential indications (non-secreting pituitary tumours, medullary thyroid carcinoma, ectopic Cushing's syndrome, diabete mellitus, Graves' ophthalmopathy, tall children and polycystic ovary syndrome) that still await further investigation. Side-effects of octreotide, particularly the formation of gallstones, should be carefully monitored.
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PMID:[Therapeutic use of somatostatin analogues in endocrinology]. 136 50

In 77 percent of patients suffering from a malignant carcinoid syndrome, administration of the somatostatin analog, octreotide (SMS 201-995, Sandostatin) induced clinical improvement coupled with a decrease in 24-hour urinary 5-hydroxyindole acetic acid (5-HIAA). This finding prompted an evaluation to determine the correlation between the presence of somatostatin receptors in tumor tissue and the response to octreotide in patients with advanced, metastatic, neuroendocrine tumors. In tissues of 31 tumors (20 carcinoid, eight islet-cell carcinoma, three medullary thyroid carcinomas), the presence of somatostatin receptors was analyzed by binding of the somatostatin analog 125I-Tyr3-SMS 201-995 and autoradiography. Receptors were detected in 16 of 20 samples of carcinoid tissues; all but one patient with receptor-positive tumors improved clinically after treatment with octreotide, and the urine 5-HIAA level was reduced a median of 63 percent (range, 39-94 percent) compared to values before treatment. Of the receptor-negative carcinoid patients, only one showed clinical improvement, which was minimal, and there was a negligible reduction in 5-HIAA after octreotide therapy. All eight patients with metastatic islet-cell carcinomas were positive for somatostatin receptors. Symptomatic improvement and a > 50 percent decrease in the level of at least one of the pathologically elevated marker hormones was seen in all eight. None of the three patients with medullary carcinoma of the thyroid had a decrease in calcitonin, and all three were initially somatostatin receptor-negative. We conclude that the presence of somatostatin receptors in malignant neuroendocrine tumor tissue appears to correlate with the response to octreotide therapy. Analysis of somatostatin receptors in malignant neuroendocrine carcinoma tissue should be included in future prospective clinical trials of this synthetic peptide.
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PMID:The presence of somatostatin receptors in malignant neuroendocrine tumor tissue predicts responsiveness to octreotide. 136 90

Medullary thyroid carcinoma associated diarrhoea can be disabling. A 75-yr-old man with metastatic medullary thyroid carcinoma and refractory diarrhoea is described. Subcutaneous administration of the somatostatin analogue, octreotide, 100 micrograms thrice daily, resulted in a sustained improvement in diarrhoea and disappearance of faecal incontinence without reducing calcitonin levels. Octreotide therapy should be considered as symptomatic treatment for otherwise refractory diarrhoea associated with medullary thyroid carcinoma.
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PMID:Octreotide for medullary thyroid carcinoma associated diarrhoea. 143 61

The multiple endocrine neoplasia (MEN) syndromes are well-defined disorders characterized by familial inheritance of specific endocrine tumors. The parathyroid, endocrine, pancreas, and pituitary tumors of MEN-1 are described by frequency and symptomatology. The effectiveness of surgery, symptomatic therapy, and panendocrine suppression by the somatostatin congener octreotide are discussed. Evidence indicates that the MEN-1 gene is located on chromosome 11 and tightly linked markers can help identify family members at risk for inheriting the gene. In MEN-2, the effectiveness of biochemical screening for thyroidal C-cell neoplasms and early thyroidectomy are described. New imaging techniques have been developed to identify medullary thyroid carcinoma and pheochromocytoma in MEN-2. Genetic analysis has identified markers on chromosome 10 closely linked to the MEN-2a gene, allowing better identification of family members likely to develop the syndrome.
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PMID:Multiple endocrine neoplasia. 167 23

This report describes the concomitant occurrence of a somatostatin-rich duodenal carcinoid, a medullary thyroid carcinoma and a diffuse adrenal medullary hyperplasia in a patient with von Recklinghausen's disease. A 50-year-old Japanese man died from lung metastasis of a malignant schwannoma. In addition to extensive viscero-cutaneous neurofibromatosis, two different types of neuroendocrine tumors were found in the duodenum and thyroid gland at autopsy. The duodenal tumor, which was located in the second portion, showed the histologic appearance of a carcinoid tumor with glandular differentiation and psammoma-bodies. Immunohistochemically the tumor cells were intensely positive for somatostatin. The thyroid tumor was composed of nests of tumor cells arranged in an endocrine pattern, and showed immunoreactivity for calcitonin. A review of the literature revealed no previously reported case of concomitant occurrence of duodenal somatostatinoma and medullary thyroid carcinoma in a single patient with von Recklinghausen's disease. Morphometric analysis of adrenal glands disclosed the presence of diffuse medullary hyperplasia. Thus, the present case exhibited a similarity in some respects with multiple endocrine neoplasia (MEN) syndrome, Type IIa or IIb.
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PMID:von Recklinghausen's disease associated with somatostatin-rich duodenal carcinoid (somatostatinoma), medullary thyroid carcinoma and diffuse adrenal medullary hyperplasia. 168 37

In primary cultures of canine enteric endocrine cells, fatty acids directly stimulated the release of neurotensin-like immunoreactivity (NTLI). This stimulatory effect was cell specific, selective for long-chain unsaturated fatty acids, and stereospecific. Saturated fatty acids of comparable chain length and trans isomers of long-chain unsaturated fatty acids had no effect on basal NTLI secretion. NTLI release in response to oleic acid (cis-11) was dose dependent with an apparent EC50 of 37 +/- 0.18 microM. Cyclooxygenase inhibitors had no effect on fatty acid-stimulated NTLI release, indicating the response was not mediated by the production of active arachidonic acid metabolites. Somatostatin (100 nM) inhibited maximal oleic acid-stimulated NTLI release by 92%. Long-chain unsaturated fatty acids also selectively and stereospecifically stimulated an increase in the mobilization of [Ca2+]i to 313.5 +/- 28.6% of resting [Ca2+]i. Staurosporine, an inhibitor of protein kinase C, dose dependently inhibited oleic acid-stimulated NTLI release with an IC50 value of 22 +/- 0.4 nM. Long-chain unsaturated fatty acids had no effect on basal NTLI secretion from rat pheochromocytoma cells and medullary thyroid carcinoma cells, two clonal lines that express NTLI. The cell-specific, selective stereospecific, and inhibitable action of fatty acids on NTLI secretion suggests that the effect of fatty acids on enteric endocrine cells is indicative of a receptor-mediated mechanism.
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PMID:Fatty acids stereospecifically stimulate neurotensin release and increase [Ca2+]i in enteric endocrine cells. 188 96


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