Schäfer J, Baumeister H, Lorenz A, Meyerhof W
Department of Molecular Genetics, German Institute of Human Nutrition and University of Potsdam, Potsdam-Rehbrücke, FRG.
Z Ernahrungswiss. 1998;37 Suppl 1:75-9.
Somatostatin and its receptors are widely distributed in the central nervous system and peripheral tissues including those of the gastrointestinal tract (GI tract). The expression patterns of the five known SSTR genes have been analysed in detail by reverse transcription polymerase chain reaction amplifications and in situ hybridizations using tissues dissected from different parts of rat stomach and gut. While SSTR1 mRNA is present at relatively high amounts throughout the gastrointestinal tract, the levels of SSTR2, 3 and 4 mRNAs vary in different regions and SSTR5 mRNA has not been detected. In situ hybridizations revealed the presence of SSTR3 mRNA in enterocytes and in neurons of the myenteric and submucous plexus. These findings are consistent with a role of SSTR3 in the observed somatostatin-mediated inhibition of acetylcholine release from myenteric neurons and of secretomotor neuron activity in the submucous plexus. Sequence analyses of the SSTR1 gene promoter revealed the absence of the canonical TATA and CAAT motifs and the presence of a variety of potential binding sites for transcriptional regulators. Among these are binding sites for GCF, AP-2, AP-4, response elements for somatostatin (SOM-RE), epidermal growth factor (EGF-RE) and cytocines (GAS and NFIL) as well as for tissue-specific factors such as Pit-1 (pituitary) and IDX-1 (pancreatic cells). Mobility shift assays have confirmed that nuclear proteins of pancreatic RIN1046-38 and pituitary GH3 tumour cells bind to oligonucleotides containing the overlapping Pit-1 and IDX-1 binding sites. Thus, the Pit-1/IDX-1 sites may be critical for the activation of the SSTR1 gene in these cell-types.
生长抑素及其受体广泛分布于中枢神经系统和外周组织，包括胃肠道组织。通过逆转录聚合酶链反应扩增和原位杂交，使用从大鼠胃和肠道不同部位解剖的组织，对五个已知的SSTR基因的表达模式进行了详细分析。虽然SSTR1 mRNA在整个胃肠道中含量相对较高，但SSTR2、3和4 mRNA的水平在不同区域有所不同，且未检测到SSTR5 mRNA。原位杂交显示SSTR3 mRNA存在于肠上皮细胞以及肌间神经丛和黏膜下神经丛的神经元中。这些发现与SSTR3在观察到的生长抑素介导的抑制肌间神经丛中乙酰胆碱释放和黏膜下神经丛中分泌运动神经元活性中的作用一致。SSTR1基因启动子的序列分析显示，缺乏典型的TATA和CAAT基序，存在多种转录调节因子的潜在结合位点。其中包括GCF、AP - 2、AP - 4的结合位点，生长抑素（SOM - RE）、表皮生长因子（EGF - RE）和细胞因子（GAS和NFIL）的反应元件，以及组织特异性因子如Pit - 1（垂体）和IDX - 1（胰腺细胞）的结合位点。凝胶迁移实验证实，胰腺RIN1046 - 38和垂体GH3肿瘤细胞的核蛋白与含有重叠的Pit - 1和IDX - 1结合位点的寡核苷酸结合。因此，Pit - 1/IDX - 1位点可能对这些细胞类型中SSTR1基因的激活至关重要。
