Mechanism of transcriptional regulation of the rat somatostatin receptor sst2 and sst5 genes.

Somatostatin不仅仅是内分泌和外分泌地区荷尔蒙保密的抑制剂，但也是大脑中的神经调节剂，对五种Somatostatin受体介导的影响（Sst 1 -5）。We previously reported that the sst5 and sst2 are major subtypes expressed in normal rat pituitaries and that sst2 dominates extremely over sst5 due to the decrease of sst5 mRNA expression in the pituitaries and that sst2 dominates extremely over sst5 due to the decrease of sst5 mRNA expression in the pituitaries from the rat treated with estrogen chronically。本研究的目标是了解Sst 2和Sst 5的转录规则的机制。结果是：（1）大鼠Sst 2和Sst 5基因被克隆和测序的5个基因。Both genes contained single intron at the 5-D11-untranslated region and lack the TATA and CCAAT boxes in the proximal upstream region of the transcription start sites。（2）对删除结构的促进者分析 ... More the 5イD11エD1-flanking region fused with a reporter gene demonstrated that the transcriptional regulatory elements in the proximal region is important for the full promoter activity of both genes。（3）竞争性凝胶移位测定和瞬态转染测定演示，其中两个Sp1和CRE站点都是必要的，用于sst 2gene的全部促进者活动，而两个Sp1站点都是相对的，用于sst 5gene的促进者活动。Sp1和CRE站点的反作用因素是Sp2和Sp3，ATF-2和c-Jun，尊重。与生物碱相关的同源蛋白Ptx 1激活了大鼠Sst 2和Sst 5基因的启动子活动的过度表达，但Pit 1did not。雌激素也增加了Sst 2的促进者活动，但减少了Sst 5的活动，可能是不可接受的。雌激素对Sst 5的影响被部分逆转与HeLa细胞中的Pit 1的共同表达。The Results of overexpression of c-jun sugested that c-jun at CRE site of the sst2 gene may mediate the activation of the sst2 promoter by estrogen receptor in the presence of estrogen. Less（低）

Somatostatin is not only an inhibitor of hormone secretion in the endocrine and exocrine glands but also a neuromodulator in the brain, effects of which are mediated by five somatostatin receptors (sst1-5). We previously reported that the sst5 and sst2 are major subtypes expressed in normal rat pituitaries and that sst2 dominates extremely over sst5 due to the decrease of sst5 mRNA expression in the pituitaries and that sst2 dominates extremely over sst5 due to the decrease of sst5 mRNA expression in the pituitaries from the rat treated with estrogen chronically. The aim of this study is to know the mechanism of transcriptional regulation of sst2 and sst5. The results were; (1) the 5ィイD11ィエD1-flanking region of the rat sst2 and sst5 genes were cloned and sequenced. Both genes contained single intron at the 5ィイD11ィエD1-untranslated region and lack the TATA and CCAAT boxes in the proximal upstream region of the transcription start sites. (2) The promoter analysis of deleted constructs of … More the 5ィイD11ィエD1-flanking region fused with a reporter gene demonstrated that the transcriptional regulatory elements in the proximal region is important for the full promoter activity of both genes. (3) Competitive gel shift assay and transient transfection assay demonstrated that both Sp1 and CRE sites were necessary for the full promoter activity of sst2 gene, and that proximal two Sp1 sites were essential for the promoter activity of the sst5 gene. The trans-acting factors of Sp1 and CRE sites were Sp2 and Sp3, and ATF-2 and c-Jun, respectively. Overexpression of the bicoid-related homeoprotein Ptx1 activated the promoter activity of the rat sst2 and sst5 genes, whereas Pit1 did not. Estrogen also increased the promoter activity of sst2 but decreased that of sst5, although no canonical ERE was observed. Estrogen effect on sst5 was partially reversed with coexpression of Pit1 in HeLa cells. The results of overexpression of c-jun suggested that c-jun at CRE site of the sst2 gene may mediate the activation of the sst2 promoter by estrogen receptor in the presence of estrogen. Less