Characterization and transcriptional regulation of the human somatostatin receptor subtype 1 gene.

Somatostatin (SRIF) exerts inhibitory effects on virtually all endocrine and exocrine secretions. At least five distinct human SRIF receptors have been identified ( SST1-SST5). Analysis of the promoter region may provide tools to understand transcriptional regulation of SSTS in various tissues, indicating specific functions. Transcriptional regulation of the human SST1 was analyzed in the present study. Total RNA from a human somatotropic pituitary tumor was reverse transcribed. 5'cDNA regions of the human SST1 were cloned using an adapted inverse PCR method. Among the 15 PCR clones analyzed, 9 demonstrated an extended 5'-utr of 266 nucleotides, determining a thymidine residue as a major transcription start site. No introns were evident in the 5'-utr region. The promoter region lacked consensus sites for TATA or CAAT boxes, YY1, or an initiator sequence, but contained two CpG islands. Different lengths of 5'-flanking regions cloned by PCR were placed upstream of the luciferase reporter gene and transiently transfected into various cell lines. The 2834 nt of the promoter region directed significant transcriptional activity in a somatotropic pituitary cell line, but neither in COS-7 monkey kidney cells nor in AtT-20 murine corticotrope cells. Transcriptional activity was not affected by incubation with various hormones. Several putative transcription factor binding sites inducing the cell-type specific activity were identified.