ABSTRACT
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.
Subject(s)
Mice , Animals , Receptors, Somatostatin/metabolism , Hematopoietic Stem Cells/metabolism , Epithelial CellsABSTRACT
OBJECTIVE: To evaluate the effectiveness of the treatment of acromegaly patients at the Federal University of Triangulo Mineiro. METHODS: Cross-sectional and retrospective study of thirty cases treated over a period of two decades. RESULTS: 17 men (56.7%) aged 14-67 years and 13 women aged 14-86 years were analyzed. Twenty-one patients underwent transphenoidal surgery, whichwas associated with somatostatin receptor ligands in 11 patients (39.3%), somatostatin receptor ligands + radiotherapyin 5 patients (17.8%), radiotherapy in 3 patients (10.7%), and radiotherapy + somatostatin receptorligands + cabergoline in 1 patient (3.6%). Additionally, 2 patients underwent radiotherapy and surgeryalone. Six patients received somatostatin receptor ligands before surgery, and 2 were not treated due to refusal and death. Nine patients have died, and 20 are being followed; 13 (65%) have growth hormonelevels o1 ng/mL, and 11 have normal insulin-like growth factor 1 levels. CONCLUSION: The current treatment options enable patients seen in regional reference centers to achieve strict control parameters, which allows them to be treated close to their homes.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Acromegaly/therapy , Adenoma/surgery , Growth Hormone-Secreting Pituitary Adenoma/surgery , Receptors, Somatostatin/metabolism , Acromegaly/blood , Adenoma/metabolism , Blood Glucose/analysis , Brazil , Combined Modality Therapy , Cross-Sectional Studies , Gigantism/blood , Gigantism/therapy , Growth Hormone/blood , Insulin-Like Growth Factor I/analysis , Ligands , Retrospective Studies , Treatment OutcomeABSTRACT
We present here the clinical and molecular data of two patients with acromegaly treated with octreotide LAR after non-curative surgery, and who presented different responses to therapy. Somatostatin receptor type 2 and 5 (SSTR2 and SSTR5), and aryl hydrocarbon receptor-interacting protein (AIP) expression levels were analyzed by qPCR. In both cases, high SSTR2 and low SSTR5 expression levels were detected; however, only one of the patients achieved disease control after octreotide LAR therapy. When we analyzed AIP expression levels of both cases, the patient whose disease was controlled after therapy exhibited AIP expression levels that were two times higher than the patient whose disease was still active. These two cases illustrate that, although the currently available somatostatin analogs bind preferentially to SSTR2, some patients are not responsive to therapy despite high expression of this receptor. This difference could be explained by differences in post-receptor signaling pathways, including the recently described involvement of AIP. Arq Bras Endocrinol Metab. 2012;56(8):501-6.
Apresentamos os dados clínicos e moleculares de dois pacientes com acromegalia tratados com octreotide LAR após cirurgia não curativa, com diferentes respostas a essa terapia medicamentosa. As expressões do receptor de somatostatina tipo 2 e 5 (SSTR2 e SSTR5) e da proteína de interação com o receptor aril hidrocarbono (AIP) foram analisadas por qPCR. Em ambos os casos, foi encontrada uma expressão elevada de SSTR2 e baixa do SSTR5. No entanto, o controle da doença foi obtido após tratamento com octreotide LAR em apenas um dos pacientes. Quando analisamos a expressão do AIP em ambos os casos, o paciente cuja doença foi controlada após a terapia medicamentosa apresentou uma expressão duas vezes maior do que a do paciente não controlado com o tratamento. Conclui-se que esses dois casos ilustram que, embora os análogos de somatostatina atualmente disponíveis se liguem preferencialmente ao SSTR2, alguns pacientes não respondem ao tratamento, apesar de uma elevada expressão desse receptor. Isso poderia ser explicado por alterações nas vias de sinalização pós-receptor, incluindo o envolvimento recentemente descrito da AIP. Arq Bras Endocrinol Metab. 2012;56(8):501-6.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Acromegaly/drug therapy , Antineoplastic Agents, Hormonal/therapeutic use , Drug Resistance, Neoplasm , Intracellular Signaling Peptides and Proteins/metabolism , Octreotide/therapeutic use , Pituitary Neoplasms/drug therapy , Acromegaly/metabolism , Pituitary Neoplasms/metabolism , Receptors, Somatostatin/metabolismABSTRACT
La gammagrafía con radiotrazadores que tienen afinidad por los receptores de somatostatina se ha convertido en metodología eficaz para el diagnóstico y estadificación de los tumores neuroendocrinos. Se presenta un caso en el cual el procedimiento radioisotópico muestra su efectividad en la localización del tumor primario.
Somatostatin receptor scintigraphy has become an important tool for diagnosis and evaluation of neuroendocrine tumors. This case report shows about the importance of the radionuclide procedure for the localization of the primary tumor.
Subject(s)
Humans , Female , Middle Aged , Carcinoma, Medullary , Carcinoma, Medullary/metabolism , Organotechnetium Compounds , Thyroid Neoplasms , Thyroid Neoplasms/metabolism , Receptors, Somatostatin/metabolism , Carcinoma, Medullary/pathology , Organotechnetium Compounds/pharmacokinetics , Thyroid Neoplasms/pathology , Octreotide/analogs & derivatives , Octreotide/pharmacokinetics , Octreotide , Radiopharmaceuticals/pharmacokinetics , RadiopharmaceuticalsABSTRACT
La marcación de péptido análogo de somatostatina DOTA-TATE (DOTA-D-phe-cys-tyr-D-trp-lys-thr-cys-thr) con 125I y sus propiedades biológicas fueron investigadas. 125I-DOTA-TATE se marco por el método de cloramina-T y se purificó por RP-HPLC a fin de aumentar su actividad especifica. La estabilidad fue evaluada por HPLC, cromatografía y electroforesis. La interacción del péptido marcado con receptores de somatostatina fue investigada usando membranas obtenidas de tejidos o de células AR42J, y por unión e internalización en cultivos celulares. El rendimiento de marcado fue mayor de 90 por ciento, el perfil de HPLC reveló dos especies radioquímicas con tiempos de retención diferentes respecto del péptido no marcado, permitiendo la obtención de una mayor actividad especifica. La máxima capacidad de unión fue de 23 por ciento y la concentración inhibitoria 50 ppor ciento fue 9 µg/mL. Se internalizó el 73 por ciento de la actividad unida en 3-4 horas. El radioconjugado presenta la capacidad de unirse específicamente a los receptores de somatostatina expresados en células tumorales viables así como en preparaciones de membranas obtenidas de tejidos animales.