Somatostatin (SST) is an inhibitory polypeptide hormone that plays an important role in a variety of biological processes. Somatostatin receptor 2 (SSTR2) is the most widely expressed somatostatin receptor. However, the specific cell types expressing Sstr2 in the tissues have not been investigated. In this study, we detected the expression pattern of SSTR2 protein in mouse at different development stages, including the embryonic 15.5 days and the postnatal 1, 7, 15 days as well as 3 and 6 months, by multicolour immunofluorescence analyses. We found that Sstr2 was expressed in some specific cells types of several tissues, including the neuronal cells and astrocytes in the brain, the mesenchymal cells, the hematopoietic cells, the early hematopoietic stem cells, and the B cells in the bone marrow, the macrophages, the type Ⅱ alveolar epithelial cells, and the airway ciliated cells in the lung, the epithelial cells and the neuronal cells in the intestine, the hair follicle cells, the gastric epithelial cells, the hematopoietic stem cells and the nerve fibre in the spleen, and the tubular epithelial cells in the kidney. This study identified the specific cell types expressing Sstr2 in mouse at different developmental stages, providing new insights into the physiological function of SST and SSTR2 in several cell types.
Mice ; Animals ; Receptors, Somatostatin/metabolism* ; Hematopoietic Stem Cells/metabolism* ; Epithelial Cells

Cortical GABAergic inhibitory neurons are composed of three major classes, each expressing parvalbumin (PV), somatostatin (SOM) and 5-hydroxytryptamine receptor 3A (Htr3a), respectively. Htr3a
Animals ; Interneurons/metabolism* ; Mice ; Neurons/metabolism* ; Parvalbumins/metabolism* ; Receptors, Serotonin, 5-HT3/genetics* ; Serotonin ; Somatostatin/metabolism*

BACKGROUNDThyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism. Somatostatin (SST) analogs work by interacting with somatostatin receptors (SSTRs). This study aimed to evaluate short-term preoperative octreotide (OCT) use in TSHoma patients and to investigate SSTR2 and SSTR5 expression and observe structural changes in tumor tissue.

METHODSWe reviewed records and samples from eight TSHoma patients treated between July 2012 and July 2015. We tested immunohistochemically for SSTR2/5 expression and examined TSHoma cells for morphological changes. Signed rank sum test was used to compare the efficacy of short-term preoperative OCT treatment.

RESULTSOCT treatment (median time: 7.9 days, range: 3-16 days; median total dose: 1.8 mg, range: 0.9-4.2 mg) led to significant decrease in all patients' thyroid hormone levels (FT3 [nmol/L]: 8.33 [7.02, 12.29] to 4.67 [3.52, 5.37] [P = 0.008]; FT4 [pmol/L]: 25.36 [21.34, 28.99] to 16.66 [14.88, 21.49] [P = 0.016]; and TSH [μU/ml]: 5.80 [4.37, 6.78] to 0.57 [0.19, 1.24] [P = 0.008]). All the eight tumor specimens expressed high SSTR2 protein levels; 5/8 expressed high SSTR5, but 3/8 that expressed low SSTR5 presented a significantly higher TSH suppression rate (P = 0.036). Electron microscopy showed subcellular level impairments, including clumped nuclear chromatin and reduced cytoplasmic volume. Golgi complexes were observed in the OCT-treated TSHoma specimens.

CONCLUSIONSOCT can control hormone levels and damage the ultrastructure of tumor cells and organelles. Short-term response to OCT may be related to SSTR5 expression. Preoperative SST analog treatment for TSHoma could be considered as a combination therapy.

Adult ; Female ; Humans ; Immunohistochemistry ; Male ; Microscopy, Electron ; Middle Aged ; Octreotide ; therapeutic use ; Pituitary Neoplasms ; drug therapy ; metabolism ; Receptors, Somatostatin ; metabolism ; Thyrotropin ; secretion

BACKGROUNDTechnetium-99m or (99m)Tc is widely used for labeling peptide in nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after binding with its receptor. This research was to study the preclinical effect of a new (99m)Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide, indirect (99m)Tc labeling of depreotide using HYNIC as a bifunctional chelator.

METHODSThe cyclopeptide, cyclo-[(N-Me) Phe-Tyr-D-Trp-Lys-Val-Hcy], the linear peptide, and [ClCH(2)-CO×b-Dap-Lys- Cys-Lys×amide] were synthesized by Fmoc solid-phase synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase synthesis. The product depreotide was isolated and purified by high performance liquid chromatography and was confirmed by mass spectrography. Depreotide was labeled with (99m)Tc through a direct labeling method, using HYNIC as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate, and through the comparative analysis selected the best mark conditions. The new (99m)Tc-HYNIC-depreotide was tested by high-performance liquid chromatography (HPLC). The internalization and externalization rates of the new (99m)Tc-HYNIC-depreotide were studied in A549 cells. Furthermore, biodistribution of the radiopeptide was studied in nude mice, bearing tumors from human lung carcinoma cells SPC-A1.

RESULTSThe molecular of synthesize depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of (99m)Tc-HYNIC-depreotide was highest at pH 6.0 and 15°C, about (70.95 ± 0.84)%. The labeling rate of the new (99m)Tc-HYNIC-depreotide rose to a peak of (20.75 ± 0.48)% at 60 minutes in A549 cells at 37°C and decreased slightly later, while it elevated gradually during the time course at 4°C and 25°C. The internalization rate of the new (99m)Tc-HYNIC-depreotide at 37°C increased gradually and reached the peak of 84.4% in 120 minutes, while the externalization rate of the new (99m)Tc-HYNIC-depreotide was always less than 20%. In mice bearing the experimental SPC-A1 tumor, the new (99m)Tc-HYNIC-depreotide demonstrated a high tumor uptake of (4.05 ± 0.04)% ID/g at 1.5 hpi and remained high ((2.51 ± 0.06)% ID/g) at 4 hpi. The tumor-to-lung activity concentration ratio (T/Lu) was very high for the new (99m)Tc-HYNIC-depreotide at all time points. So did the tumor-to-muscle activity (T/Mu) and tumor-to-blood activity concentration ratios (T/Bl).

CONCLUSIONThe findings suggested that the new (99m)Tc-HYNIC-depreotide might be a promising candidate radiopharmaceutical for imaging somatostatin receptor positive lung cancer.

Animals ; Cell Line, Tumor ; Humans ; Hydrazines ; chemistry ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Mice, Nude ; Nicotinic Acids ; chemistry ; Receptors, Somatostatin ; metabolism ; Technetium ; chemistry

OBJECTIVE: To investigate the effect of high-fat (HF) diet on the body weight and the mRNA expression of melanin concentrating hormone receptor 1 (MCHR1) and leptin receptor (OB-Rb) in the adipose tissue in rats, the two important and opposite factors in regulating the body weight. METHODS: Post-weaning rats were divided into 3 groups: the NC group were fed a normal-chow diet (NC) (13% calories from fat), the HF group with a HF-diet (47% calories from fat) and the PHF group pair-fed a HF-diet (47% calories from fat). At the end of 8th week, the gained bodyweight, the plasma melanin concentrating hormone (MCH) and leptin, and the expression levels of MCHR1 and OB-Rb in the adipose tissue were measured. RESULTS: Both the HF-diet and pair-fed HF-diet enhanced the body weight (P<0.01), plasma MCH (P<0.01) and leptin concentrations (P<0.05). In the adipose tissue, HF-diet resulted in significant increase in MCHR1 (PHF group,P<0.05) and decrease in OB-Rb mRNA levels (HF group,P<0.01; PHF group,P<0.05). No statistical difference was found between the HF group and the PHF group in terms of the aforementioned data (P>0.05). CONCLUSION Chronic intake of iso-caloric HF-diet and ad libitum HF-diet obviously results in increase in the body weight, serum leptin, and MCH concentration. Diet-induced obesity and related metabolic disorders are possibly correlated with up-regulated expression of MCHR1 and down-regulated expression of OB-Rb in the adipose tissue.
Adipose Tissue ; metabolism ; Animals ; Animals, Newborn ; Diet, High-Fat ; adverse effects ; Dietary Fats ; administration & dosage ; Hypothalamic Hormones ; blood ; Leptin ; blood ; Male ; Melanins ; blood ; Obesity ; etiology ; metabolism ; Pituitary Hormones ; blood ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Leptin ; genetics ; metabolism ; Receptors, Somatostatin ; genetics ; metabolism

OBJECTIVE: To detect the expression and relationship between somatostatin receptor 2 (SSTR2) and phosphorylated STAT3 (P-STAT3) in human olfactory neuroblastoma (ONB) and adjacent normal olfactory nerve tissue. METHOD: Immunohistochemical (IHC) staining was used to detect the expression of SSTR2 and P-STAT3 in tumor and adjacent normal olfactory nerve tissue from 11 ONB patients. RESULT: SSTR2 was mainly expressed in cell cytoplasm and the expression intensity was significantly stronger in tumor tissues than in adjacent normal tissues (P<0.01). P-STAT3 was mainly expressed in cell nuclear in tumor tissues. No expression was found in adjacent normal tissues. There was a negative correlation between the expression intensity of SSTR2 and P-STAT3 (r(s) = -0.367, P<0.05). CONCLUSION Lower expression of SSTR2 and activation of STAT3 in ONB cells might contribute to the development of ONB.
Adolescent ; Adult ; Esthesioneuroblastoma, Olfactory ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Nose Neoplasms ; metabolism ; pathology ; Receptors, Somatostatin ; metabolism ; STAT3 Transcription Factor ; metabolism ; Young Adult

OBJECTIVETo investigate the effects of SOM230, a new somatostatin analogue, on the proliferation of hepatocellular carcinoma (HCC) cell line HepG2 in vitro and in vivo, and explore the mechanism underline the necrosis of tumors.

METHODSMTT, TdT-mediated dUTP nick end labeling assay (TUNEL) and flow cytometric assay were used to measure the effects of SOM230 on the proliferation and apoptosis of HCC HepG2 cells. Nude mice bearing HCC xenografts of the HepG2 cell line were treated with SOM230 (100 microg/kg/d subcutaneously injection) and saline as a control for eight weeks. The mass and percentage of necrotic volume of the HCC xenografts in nude mice were determined. Western blot was used to detect SSTR2 in HCC xenografts. Immunohistochemical method was used to detect the expression sites of SSTR2 and VEGF in HCC xenografts. ELISA was used to detect the levels of TNFalpha.

RESULTSNo proliferation and apoptosis of HepG2 cells were induced by SOM230 in vitro (F = 0.16, P more than 0.05). The percentage of necrotic volume in SOM230 were significantly higher than that of control group (73.4%+/-7.0% vs 30.2%+/-14.0%, t = -8.02, P more than 0.01). SSTR2 was expressed in blood sinus of HCC xenografts in nude mice. There was no significance difference in the level of SSTR2 expression between SOM230 group and saline treated group. VEGF expression in xenografts was down-regulated by SOM230 treatment. SOM230 treatment did not affect the level of TNFalpha in HCC xenografts (t = -0.24, P more than 0.05).

CONCLUSIONSSOM230 can induce massive necrosis of HCC xenografts only after the blockage of blood flow through down-regulation of VEGF mediated by SSTR2.

Animals ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; Cell Proliferation ; drug effects ; Disease Models, Animal ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Hep G2 Cells ; Humans ; Immunohistochemistry ; Injections, Subcutaneous ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Random Allocation ; Receptors, Somatostatin ; metabolism ; Somatostatin ; administration & dosage ; analogs & derivatives ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays

Recently various peptide receptors which displayed the highest binding affinity and specificity with their peptide ligands by ligand-receptor have been exploited to develop drug delivery system which can directionally deliver drug to targeted cell. It is significant to study and applicate, including targeted drug delivery system mediated by bombesin receptor, somatostatin receptor, SynB3 receptor, LH-RH receptor and other peptide receptor, et al. Several small peptide fragments were selected as carriers radicals combining doxorubicin, 2-pyrrolino-DOX, methotrexate, cis-platinum, and camptothecin to form hybrid cytotoxic analogs. These highly potent cytotoxic analogs have been designed as targeted anti-tumor agents for the treatment and study of various cancers that possess receptors for the carrier peptide.
Animals ; Antineoplastic Agents ; therapeutic use ; Doxorubicin ; analogs & derivatives ; therapeutic use ; Drug Delivery Systems ; Humans ; Neoplasms ; drug therapy ; metabolism ; Oligopeptides ; metabolism ; Pyrroles ; therapeutic use ; Receptors, Bombesin ; metabolism ; Receptors, LHRH ; metabolism ; Receptors, Somatostatin ; metabolism

Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; Female ; Humans ; Liver Neoplasms ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; biosynthesis ; Receptors, Somatostatin ; biosynthesis ; classification ; genetics ; Tumor Cells, Cultured

Amino Acid Sequence ; Animals ; Antineoplastic Agents ; chemistry ; metabolism ; pharmacology ; Apoptosis ; drug effects ; Humans ; Molecular Structure ; Neoplasms ; pathology ; prevention & control ; Receptors, Somatostatin ; metabolism ; Somatostatin ; chemistry ; metabolism ; pharmacology ; Structure-Activity Relationship