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)

About one-third of acromegalics are resistant to the clinically available somatostatin analogs (SA). The resistance is related to density reduction or different expression of somatostatin receptor subtypes (SSTR). This study analyzes SSTR's expression in somatotrophinomas, comparing to SA response, hormonal levels, and tumor volume. We analyzed 39 somatotrophinomas; 49% were treated with SA. The most expressed SSTR was SSTR5, SSTR3, SSTR2, SSTR1, and SSTR4, respectively. SSTR1 and SSTR2 had higher expression in patients that had normalized GH and IGF-I. SSTR3 was more expressed in patients with tumor reduction. There was a positive correlation between the percentage of tumor reduction and SSTR1, SSTR2 and SSTR3 expression. Also, a positive correlation between SSTR2 mRNA expression and the immunohistochemical reactivity of SSTR2 was found. Our study confirmed the association between the SA response to GH and IGF-I and the SSTR2. Additionally, this finding was also demonstrated in relation to SSTR1.
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PMID:Acromegaly: correlation between expression of somatostatin receptor subtypes and response to octreotide-lar treatment. 1933 Apr 52

Somatostatin (SS14) is an important regulator of endocrine and brain function exerting its action after binding to high-affinity membrane receptor subtypes. Its diverse physiological activities include inhibition of hormone secretion from pituitary, pancreas, and gut. In the CNS, SS14 acting as a neurotransmitter/neuromodulator exerts inhibitory effects on neural function. Recently, three SS14 receptor genes, SSTR1, SSTR2, and SSTR3, have been cloned and characterized. We have cloned and characterized a novel fourth member of this gene family from a rat genomic library, SSTR4, which is expressed predominantly in neural tissue. When stably expressed in CHO-K1 cells, SSTR4 binds SS14 and SS28 with high affinity; however, the SS14 analogs SMS 201-995 and MK 678 failed to displace specific binding. High-affinity agonist binding was diminished by prior exposure to both GTPgammaS and pertussis toxin (PTX) but was not effected following agonist pretreatment, indicating that SSTR4 is coupled to a PTX-sensitive G-protein but does not desensitize. SSTR4 expressed in CHO cells is coupled by a PTX-sensitive G-protein to inhibition of adenylyl cyclase since treatment of transfected cells with SS14 resulted in the inhibition of forskolin-stimulated cAMP accumulation, an effect that was abolished by PTX treatment. The cloning of four SS14 receptor subtypes provide molecular probes for structure-function studies and for identifying those particular subtypes responsible for mediating the diverse physiological action of SS14.
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PMID:Ligand Binding and Functional Properties of the Rat Somatostatin Receptor SSTR4 Stably Expressed in Chinese Hamster Ovary Cells. 1991 29

Somatostatin receptors (SSTR) are expressed in various endocrine tumours. The expression of SSTR at the tumour cell surface confers the possibility for diagnostic imaging and therapy of tumours using radiolabeled somatostatin analogues. The majority of currently available somatostatin analogues show a higher binding affinity for the SSTR2 subtype. To date, the precise expression pattern of the SSTR subtypes 1-5 in thyroid epithelial tumours remains to be determined. We investigated the mRNA expression of SSTR1-5 in benign and malignant epithelial thyroid tumours [20 cold thyroid nodules (CTNs), 20 toxic thyroid nodules (TTNs), 20 papillary, 20 follicular, and 5 anaplastic carcinomas (PTCs, FTCs, ATCs, respectively)] and compared them to normal surrounding thyroid tissues. Four out of five SSTR subtypes were detected in malignant thyroid tumours, benign neoplasia, and normal surrounding tissue with a predominant expression of SSTR2 and SSTR5, and a weak expression of SSTR1 and SSTR3. Weak SSTR4 mRNA expression was detected in some PTCs. Compared to normal thyroid tissue, SSTR2 was significantly upregulated in PTC and ATC. In addition significant upregulation of SSTR3 was found in PTC. SSTR5 mRNA expression was increased in PTC and FTC and significantly decreased in CTN and TTN compared to normal thyroid tissue. SSTR2 is the predominant subtype in thyroid epithelial tumours with a high expression pattern, in particular, in PTC . Perspectively, the expression of distinct SSTR in thyroid epithelial tumours might represent a promising avenue for diagnostics and therapy of advanced thyroid cancer with somatostatin analogues.
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PMID:Somatostatin receptor subtype expression in human thyroid tumours. 2009 70

Somatostatin analogues (SAs) are potential anticancer agents. This study was designed to investigate the expression of somatostatin receptors (SSTRs) in melanoma cells and the effect of two SAs on cell proliferation and viability. Eighteen primary and metastatic human cutaneous melanoma cell lines were treated with octreotide and SOM230. Expression of SSTR1, SSTR2, SSTR3 and SSTR5 was assessed by real-time polymerase chain reaction. Proliferation, viability and cell death were assessed using standard assays. Inhibition was modelled by mixed-effect regression. Melanoma cells expressed one or more SSTR. Both SAs inhibited proliferation of most melanoma cell lines, but inhibition was < 50%. Neither SA affected cell viability or induced cell death. The results suggest that melanoma cell lines express SSTRs. The SAs investigated, under the conditions used in this study, did not, however, significantly inhibit melanoma growth or induce cell death. Novel SAs, combination therapy with SAs and their anti-angiogenic properties should be further investigated.
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PMID:Expression of somatostatin receptors in human melanoma cell lines: effect of two different somatostatin analogues, octreotide and SOM230, on cell proliferation. 2014 79

Somatostatins (SSs) and somatostatin receptors (SSTRs) play important roles in the growth, development and metabolism of vertebrates. In the present study, four SSTRs were isolated from orange-spotted grouper (Epinephelus coioides), a coral fish of high commercial value cultivated in Southeast Asia. Phylogenetic tree analysis grouped the four SSTRs as two distinct groups of SSTR1 and SSTR2/3/5. Four SSTRs exhibited high homology across the vertebrates. The expression of four grouper SSTR mRNAs was studied in 11 tissues. The highest level of SSTR1 mRNA was found in forebrain. The mRNAs of SSTR2 and SSTR3 were highly expressed in pituitary, forebrain and liver. The levels of SSTR5 mRNA were low in most tissues except for pituitary and intestine. The expression of four grouper SSTR mRNAs was investigated in seven embryonic stages and five early larval development stages. The highest levels of SSTR1 and 2 mRNAs appeared during hatching, while the highest levels of SSTR3 and 5 mRNAs were found in brain vesicle stage. Intraperitoneal injection of SS14 significantly increased the levels of all four SSTR mRNAs in pituitary and SSTR1, 3 mRNAs in liver in a dose-dependent manner, but no effect on SSTR2 and 5 in liver. These observations contribute to the understanding of the evolution of SSTR family and offer information on structure, distribution and function of fish SSTRs.
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PMID:Comparative analyses of sequence structure, evolution, and expression of four somatostatin receptors in orange-spotted grouper (Epinephelus coioides). 2034 29

Somatostatin analogs (SSA) are the standard diagnostic and treatment tools in the clinical management of patients with neuroendocrine tumors (NETs) expressing somatostatin receptors (SSTRs). Although symptomatic and biochemical control is obtained with SSA in the majority of functional NETs, antineoplastic effects of SSA are partial and of limited duration. The aim of this study was to quantify expression levels of five SSTR subtypes (SSTR1-SSTR5) and correlate them with the clinical outcomes of patients with NETs who underwent SSA therapy. The expression levels were analyzed using real-time polymerase chain reaction in a series of 22 metastatic NETs with a median time of 10 months on the SSA therapy (range 2-82 months). The median duration of disease stabilization in patients who developed progression (n = 14) was 9 months (range 3-92 months). The median survival period for all patients was 44 months (range 3-175 months). According to RECIST criteria, one (5%) partial objective tumor response was obtained, disease stabilization was achieved in 10 (45%) patients, and progressive disease was observed in 11 (50%). Analysis of mRNA expression of the SSTR subtypes showed that SSTR2 and SSTR5 were expressed in all of the studied NETs; SSTR1 and SSTR4 in all but 3 tumors (86%); and SSTR3 in only 10 NETs (49%). Interestingly, our preliminary data suggest that only the levels of SSTR4, though it has the lowest affinity for SSA of all SSTR subtypes, were significantly associated with the stabilization of disease during SSA therapy (p = 0.0357). These levels correlated with time to progression (p = 0.0015) and overall survival (p = 0.0017) in NET patients.
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PMID:Gene expression of somatostatin receptor 4 predicts clinical outcome of patients with metastatic neuroendocrine tumors treated with somatostatin analogs. 2042 38

Oncogenic osteomalacia (OOM) is a rare disease characterized by renal phosphate wasting and osteomalacia and is caused by the secretion of fibroblast growth factor 23 (FGF-23) from causative tumors. Scintigraphy with octreotide, which binds to somatostatin receptors (SSTRs), is a useful way to locate causative tumors in OOM patients. However, the therapeutic effects of octreotide acetate are still controversial. Two OOM patients were administered octreotide acetate intramuscularly. Ten causative OOM tumors, including two resected from the patients participating in the octreotide administration study, were examined for expression of genes encoding SSTRs by quantitative real-time RT-PCR and immunohistochemistry. Octreotide therapy did not improve hypophosphatemia in either case, despite temporal decreases in FGF-23 levels in one patient. The mean expression levels of SSTR1, SSTR3, and SSTR5 were similar in the OOM and non-OOM tumors. Expression of SSTR2 was significantly higher in the OOM tumors than in the non-OOM tumors. Immunohistochemical examinations revealed the presence of SSTR2A, SSTR2B, and SSTR5 in both the OOM and non-OOM tumors. The expression of SSTR genes in OOM tumors contributes to positive imaging using octreotide scintigraphy. However, the levels of SSTRs seem to be insufficient for the octreotide therapy to improve hypophosphatemia. Further studies are needed to clarify the mechanisms by which FGF-23 secretion from OOM tumors is suppressed by octreotide acetate.
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PMID:The levels of somatostatin receptors in causative tumors of oncogenic osteomalacia are insufficient for their agonist to normalize serum phosphate levels. 2045 78

Somatostatin (SST) is a regulatory peptide hormone that acts through five different G protein-coupled receptors (SSTR1-5). Whereas expression of all five SSTR subtypes in epidermis has been shown, the biological relevance of the SST/SSTR system in the skin is completely unknown. We show here that SST is expressed in human skin and is present in a subset of Merkel cells and dendritic cells as well as in keratinocytes. We focused further on the somatostatin receptor subtype 3 (SSTR3) and its interacting protein MUPP1, as both were found to be localized at cellular junctions in epidermal keratinocytes. MUPP1 is a component of tight junctions (TJs); these cell-cell junctions contribute to barrier function of the paracellular pathway in cultured keratinocytes. We provide evidence that SSTR3 and MUPP1 interact in primary cultured human keratinocytes at high Ca(2+) conditions. Interestingly, SST, presumably via SSTR3/MUPP1, regulates TJ permeability in cultured keratinocytes. During long-term treatment of human keratinocytes, SST also affects the expression of distinct TJ proteins such as claudin-4. Our data are the first example of a peptide hormone regulating TJ functionality and composition in human keratinocytes, suggesting that control via peptide hormones provides the possibility to regulate the TJ barrier characteristics of the skin.
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PMID:Somatostatin regulates tight junction function and composition in human keratinocytes. 2062 40

The aim of the study is to examine the tissue expression and localization of the somatostatin receptors (SSTRs) in prostate cancer (PCa) with neuroendocrine (NE) differentiation. The five SSTR subtypes (SSTR1 to 5) were evaluated immunohistochemically in the secretory cells of normal-looking epithelium (Nep), high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa in 20 radical prostatectomies (RPs) with Gleason score 3+3=6 acinar PCa; 20 RPs with GS 4+4=8 and 4+5=9 PCa; and 20 RPs with PCa with NE differentiation. The basal cells were evaluated in Nep and HGPIN. In all groups the stromal smooth muscle and endothelial cells were also analyzed. Concerning the secretory cells, (i) the greatest mean proportions of cells with strong cytoplasmic staining in PCa were seen for SSTR2, mainly in the group of RP with NE differentiation, and for SSTR4 in all three groups; the mean values in HGPIN were intermediate between Nep and PCa; (ii) Membrane staining was seen for SSTR3 and SSTR4; the mean percentages of positive cells, higher in SSTR3 than in SSTR4, decreased from Nep to HGPIN and PCa in all three RP groups; in the latter two, the mean percentages were similar; and (iii) Nuclear staining was seen with SSTR4 and SSTR5; for SSTR4, the mean percentages in the PCa of the three groups were higher than in HGPIN and Nep, the highest proportion being with PCa with NE differentiation. Concerning the basal cells, in Nep the mean proportions of cells with strong staining intensity were greater for SSTR1 and SSTR3 than for the other subtypes, the lowest being with SSTR2; in HGPIN the highest mean propositions of positive cells was with SSTR3, the proportions in the three RP groups being similar. Concerning the stromal smooth muscle and endothelial cells, the highest mean values being in SSTR1 and the lowest in SSTR5; for the former subtype the highest proportion of endothelial cells with strong intensity was seen in the RP NE group. In conclusion, this immunohistochemical study expands our knowledge on the expression and localization of five SSTRs in the various tissue components in the prostate with PCa with NE differentiation, compared with conventional PCa. Typing somatostatin receptor expression in NE tumours could be of relevance to target somatostatin analogue-based diagnostic approach and treatment.
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PMID:Immunohistochemical expression and localization of somatostatin receptor subtypes in prostate cancer with neuroendocrine differentiation. 2064 46

Somatostatin is well known as an inhibitor of growth hormone release from the anterior pituitary. Its effects are exerted via 5 subtypes of receptors, which are named SSTR1 through 5. We recently reported that intracerebroventricular (ICV) injection of somatostatin stimulates feeding behavior in chicks. However, the specific receptors which mediate this orexigenic effect have not been identified in chicks. Thus, the purpose of the present study was to identify the receptor subtypes involved in somatostatin-induced feeding using 5 somatostatin analogs. Chicks that received vapreotide and octreotide (less than 3nmol), which are agonist of SSTR2 and SSTR5, increased their food intake. Additionally, chicks ICV injected with BIM23056 or L-817,818 (SSTR3 and SSTR5 agonists, respectively) also had increased food intake. However, ICV injection of the SSTR4 agonist L-803,087 did not cause an orexigenic effect, suggesting that SSTR4 might not be important in somatostatin-induced feeding behavior. In summary, results from this study may be interpreted as SSTR2, SSTR3 and SSTR5 are related to somatostatin-associated feeding behavior in chicks.
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PMID:Feeding responses to central administration of several somatostatin analogs in chicks. 2082 22


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