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

Somatostatin-like immunoreactivity (SRIF-LI) has previously been demonstrated immunohistochemically in rat thyroid parafollicular cells. Studies were therefore performed to determine whether SRIF-LI was present in a transplantable medullary carcinoma of the thyroid (MCT) in the WAG/Rij strain of rat. SRIF-LI was found in MCT in significantly higher concentrations than in normal thyroid tissue. Thyroid and MCT SRIF-LI showed parallelism with the synthetic SRIF and RIA displacement curves and coeluted with synthetic SRIF on immunoaffinity chromatography. On gel filtration, thyroid SRIF-LI and the major peak of MCT SRIF-LI coeluted with synthetic SRIF. SRIF-LI of a larger molecular size was also present in the MCT. MCT and thyroid SRIF-LI coeluted with synthetic SRIF on high pressure liquid chromatography. MCT SRIF-LI purified by affinity chromatography was equipotent to synthetic SRIF in inhibiting dibutyryl cAMP-stimulated GH release by rat pituitary cells in monolayer culture. Serum SRIF-LI was elevated in tumor-bearing rats and showed characteristics similar to those of MCT SRIF-LI and synthetic SRIF on affinity and high pressure liquid chromatography (HPLC). Tumor-bearing rats showed diminished secretion of insulin after orally administered glucose and impaired secretion of GH in response to pentobarbital compared to normal control rats. The results indicate that SRIF-LI is produced in excessive quantities by a transplantable rat MCT and impairs the secretion of GH and insulin. The immunological, chromatographic, and biological properties of MCT SRIF-LI suggest that it is indistinguishable from synthetic SRIF.
 ...
PMID:Somatostatin-like immunoreactivity in transplantable medullary carcinoma of rat thyroid: partial chromatographic and biological characterization. 610 40

Thyroid tissue from 18 consecutive cases of Hashimoto's thyroiditis treated surgically were stained immunohistochemically for neurone specific enolase (NSE), somatostatin, calcitonin and thyroglobulin. Cells staining for NSE and somatostatin were present in 14 cases. In four cases large numbers of cells including oxyphil cells stained for NSE. Consecutive sections showed an identical staining pattern of these cells for somatostatin. Sections stained for calcitonin showed few or no positively staining cells. There were moderate numbers of NSE and somatostatin-containing cells in five of the cases, occasional cells in five and none in four cases. Electron microscopy confirmed neurosecretory-like granules within positively staining cells. Somatostatin is known to inhibit T3 and T4 production or release from thyroid cells by a direct action. We suggest, in Hashimoto's disease, somatostatin in paracrine cells serves as a local inhibitory neuroendocrine effector and could be causally related to the hypothyroid state.
 ...
PMID:Somatostatin: a paracrine contribution to hypothyroidism in Hashimoto's thyroiditis. 612 55

A guinea pig showing spontaneous abnormalities in both calcitonin and somatostatin syntheses was found. Thyroid C cells revealed an almost complete absence of secretory granules immunoreactive to calcitonin and somatostatin. Instead, vesicular inclusions of various sizes, which exhibited positive immunoreactions for calcitonin and somatostatin, were found in some C cells. There were several C cells with enlarged and eosinophil cytoplasm, showing a hyaline degeneration. The number of C cells per thyroid and their distribution pattern were not different from those of normal controls. Follicular cells did not exhibit any detectable changes, whereas parathyroid glands were somewhat degenerated.
 ...
PMID:The spontaneous loss of calcitonin and somatostatin in thyroid C cells of a guinea pig. 615 83

The addition of thyroid hormone to cultures of GH3 or GH4C1 pituitary tumor cells maintained in medium with hypothyroid serum decreased the concentration of specific receptors for TRH. The relationship between thyroid hormone effects on TRH receptors and TRH responses was examined by testing the concentration dependence, time course, and specificity of these changes. The concentrations of T3 giving half-maximal decreases in [3H]TRH binding and inhibition of the PRL response to TRH were 0.20 and 0.24 nM, respectively. TRH stimulated the rate of [3H]uridine uptake by 50% in cultures incubated without added T3 but did not increase [3H]uridine uptake in cells incubated with thyroid hormone. The PRL response to TRH was substantially inhibited 12 h after the addition of T3, and the uridine uptake response was completely blocked in 8 h. Two other stimuli of PRL secretion, sodium butyrate and isobutylmethylxanthine, were effective in the presence or absence of T3. Thyroid hormone did not reduce the specific binding of either [125I-Tyr1]somatostatin or [125I]iodoepidermal growth factor. Somatostatin decreased the secretion of GH and PRL by pituitary tumor cells grown with or without T3. The data show that the effects of thyroid hormones on TRH receptors are specific and suggest that regulation of receptor concentrations may be the direct cause of thyroid hormone regulation of pituitary responsiveness to TRH.
 ...
PMID:Mechanism of thyroid hormone inhibition of thyrotropin-releasing hormone action. 625 85

Somatostatin (SRIF) immunoreactivity has been frequently reported in tumor tissues of cell types, belonging to the APUD system, including medullary thyroid carcinoma (MTC). However, the value of SRIF as a plasma tumor marker for MTC is controversial. We have measured SRIF plasma levels in 35 patients with different stages of MTC to evaluate the use of SRIF as a plasma tumor marker compared to the current "gold standard" calcitonin (CT). The median SRIF value in healthy controls was 36.5 pg/mL, the upper limit of normal was defined at the controls. The median value was 28 pg/mL (p = 0.37, Mann-Whitney U test). Five patients in the control group and three in the MTC group had SRIF levels that exceed the 95th percentile. SRIF and CT levels correlated only weakly (0.38), as determined by the Spearman rank order correlation test. Pentagastrin stimulation led to a diagnostic increase in SRIF levels in only one of five MTC patients. During selective venous catheterization, diagnostic gradients for CT, allowing tumor localization, could be demonstrated, whereas measurement of SRIF levels did not aid in tumor detection. Although SRIF immunostaining may be valuable as an additional marker in the histochemical diagnosis of MTC, SRIF has no value as a plasma tumor marker in the diagnosis of this disease.
Thyroid 1995 Aug
PMID:Evaluation of somatostatin as a plasma tumor marker in medullary thyroid carcinoma. 748 70

We examined the effects of thyroid-stimulating hormone (TSH) on basic fibroblast growth factor (basic FGF) expression in isolated ovine thyroid follicles in vitro, and the effects of exogenous basic FGF on thyroid growth and function, to elucidate the significance of increased basic FGF expression during TSH-induced rat thyroid hyperplasia in vivo. Primary cultures of ovine thyroid follicles were maintained in serum-free Ham's modified F-12M medium containing transferrin, somatostatin, and glycyl-histidyl-lysine (designated 3H) with or without basic FGF alone, or in combination with TSH (100 microU/mL) and cortisol (10 nM). Following 48 h incubation, cells were harvested and total RNA prepared for the detection of basic FGF mRNA using Northern blot analysis and ribonuclease protection assay. Basic FGF in the cytoplasm and extracellular matrix fractions was quantified by radioimmunoassay. Basic FGF mRNA transcripts of 3.7, 3.0, and 2.2 kb, respectively, were found in thyroid follicles cultured in 3H medium, and the abundance of each increased between 2- and 3-fold following incubation with 10-50 microU/mL TSH, although higher concentrations of TSH were less effective. Similar results were seen using a more sensitive ribonuclease protection assay. Cells cultured in control, 3H medium contained 2.4 +/- 0.5 fmol immunoreactive basic FGF/micrograms cell DNA within the cytoplasm and 21.1 +/- 1.5 fmol/micrograms DNA within the extracellular matrix (mean +/- SD, n = 6). A significant increase (p < 0.05) in basic FGF content was seen in both cell compartments following incubation with 50 or 100 microU/mL TSH, while 250 microU/mL was less effective.(ABSTRACT TRUNCATED AT 250 WORDS)
Thyroid 1994
PMID:Basic fibroblast growth factor (basic FGF) in isolated ovine thyroid follicles: thyrotropin stimulation and effects of basic FGF on DNA synthesis, iodine uptake and organification, and the release of insulin-like growth factors (IGFs) and IGF-binding proteins. 751 16

Since the identification of somatostatin receptors on lymphocytes, orbital infiltration with mononuclear cells in Graves' ophthalmopathy has provided a rationale for receptor imaging with the radiolabeled somatostatin analog Octreotide. In 40 patients with Graves' ophthalmopathy and 10 controls, 110 MBq indium-Octreotide were administered i.v., and scans were performed at 4 and 24 h after injection. An uptake ratio between the orbits and the brain was determined. In 20 ophthalmophathy patients, magnetic resonance imaging (MRI) of the orbits was performed and the T2 relaxation time was measured within the rectus muscles. Compared to controls (4 h Octreotide uptake: median 6.0 counts/pixel/MBq, orbit/brain ratio 5.6), ophthalmopathy patients showed a 2- to 3-fold increased uptake (15.8 counts/pixel/MBq vs controls p = 0.0032; ratio 12.6, vs controls p = 0.003). When considering patients with active disease only, a higher uptake was registered (16.8 counts/pixel/MBq vs controls p 0.0048, ratio 15.6 vs controls p = 0.0006). Untreated patients showed a markedly higher uptake (23 counts/pixel/MBq) compared to patients receiving steroid therapy (12.6, p = 0.001). MRI of the orbit revealed a correlation between T2 relaxation time of the eye muscles and orbital uptake of Octreotide (p < 0.001).
Thyroid 1995 Apr
PMID:Role of octreoscan and correlation with MR imaging in Graves' ophthalmopathy. 764 69

Octreotide is a long-acting somatostatin analog that inhibits cell growth and hormone secretion. It has been successfully used in the management of a variety of endocrine tumors (i.e., acromegaly, carcinoid tumors, gastrinomas). In vitro, octreotide suppresses adenylate cyclase activity, DNA synthesis, and cell growth in cultured thyroid cell lines. Previous studies examining the use of octreotide in the treatment of medullary thyroid cancers, in vivo, report symptomatic improvement from tumor-related hormonal hypersecretion; however, octreotide's ability to suppress tumor growth was limited. In the present study, we examine the efficacy of long-term octreotide administration in six subjects with metastatic thyroid carcinoma, including Hurthle cell (one subject), medullary (one subject) and papillary or mixed papillary/follicular cancer (four subjects). All of the subjects had documented recurrences of their thyroid tumors despite appropriate therapy, and were considered to be untreatable by conventional therapeutic modalities (i.e., radioiodine or surgery). Subjects were monitored while receiving relatively high doses (4 mg daily) octreotide subcutaneously for up to 12 months. Octreotide therapy was very well tolerated; mild gastrointestinal symptoms persisted throughout treatment in one subject. Octreotide did not significantly decrease tumor markers (e.g., thyroglobulin, calcitonin, carcinoembryonic antigen). The carcinomas progressed during treatment, as evidenced by an increase in the size and/or number of metastatic lesions. In summary, in this small series subcutaneous octreotide administration did not appear to be efficacious in the management of advanced thyroid cancers.
Thyroid 1994
PMID:Octreotide therapy in advanced thyroid cancer. 771 6

Recent evidence has shown that endocrine tumors are under an endocrine and an immune regulation, and that biotherapies with interferon or the long-acting somatostatin analog octreotide may be effective in the control of tumor growth and clinical symptomatology. Within the biotherapies of tumors, interleukin-2(IL-2) has appeared to play an essential role in the antitumor immune response. Despite its important antitumor role, very few studies have been carried out to investigate the possible use of IL-2 in the treatment of advanced endocrine tumors. Its potential toxicity would represent the main limiting factor for the clinical experiments with IL-2. Our previous studies have shown that the pineal hormone melatonin (MLT) may amplify the antitumor activity of IL-2, either through immunomodulating mechanisms or through a direct cytostatic activity by inhibiting tumor growth factor production. On this basis, we have performed a phase II pilot study with low-dose IL-2 plus MLT in 14 patients with untreatable endocrine tumors because of disseminated disease, lack of response to previous standard biotherapies or chemotherapies, or tumors for whom no effective therapy is available. Thyroid cancers, carcinoid and endodrine pancreatic tumors were the most frequent neoplasms. IL-2 was given at 3 million IU/day s.c. at 8 p.m. for 6 days/week for 4 weeks, corresponding to one cycle. MLT was given orally at 40 mg/day at 8 p.m. every day. In nonprogressed patients, a second cycle was given after a 21-day rest period. Patients were considered as evaluable when they received at least one complete cycle, and 12 patients were fully evaluable. According to WHO criteria, a partial response was achieved in 3/12 (25%) patients (carcinoid tumor: 1; neuroendocrine lung tumor: 1; pancreatic islet cell tumor: 1). Another patient with gastrinoma had a more than 50% reduction of tumor markers. Toxicity was low in all patients. This preliminary study suggests that low-dose IL-2 immunotherapy in association with the pineal hormone MLT may constitute a new well-tolerated and potentially active therapy of untreatable advanced endocrine tumors.
 ...
PMID:Immunoendocrine therapy with low-dose subcutaneous interleukin-2 plus melatonin of locally advanced or metastatic endocrine tumors. 785 78

Thyroid C-cells have the capacity to produce a variety of peptides, as do C-cell tumors. The cellular content of one such peptide, somatostatin, is restricted to a minority of C-cells in rat and human. We set out to clarify whether the synthesis of somatostatin is equally restricted and to study changes that occur in somatostatin synthesis with age. We used immunocytochemistry to localize somatostatin and calcitonin in conjunction with in situ hybridization, using digoxigenin-labeled oligoprobes to localize somatostatin and calcitonin mRNAs in serial sections of formalin-fixed, paraffin-embedded rat thyroid, and correlated peptide and mRNA content in individual cells. All C-cells synthesize and store calcitonin, and somatostatin synthesis, as shown by mRNA content, is limited to the subset of cells containing immunoreactive somatostatin. The numbers of C-cells in general and of the subset synthesizing somatostatin increase between juvenile and adult animals, but the somatostatin cells remain confined to a small area of the gland. These findings support the proposal that somatostatin production is not facultative, but that C-cells differentiate into two distinct subsets of cells, only one of which synthesizes and stores somatostatin.
 ...
PMID:Synthesis and storage in rat thyroid C-cells. 791 5


<< Previous 1 2 3 4 5 6 7 8 Next >>