Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin exerts inhibitory effects on virtually all endocrine and exocrine secretions. The somatostatin receptor subtype 2 (sst2) acts as a critical molecule for growth hormone regulation and cell proliferation. We investigated the structure and regulation of the human sst2 gene. A genomic clone including the sst2 gene was isolated, 1.5 kb of the promoter was sequenced and putative transcription factor binding sites were identified. The transcription start site was located 93 nucleotides upstream of the translation start site. The nucleotide sequences of the complete gene and 0.5 kb of 3' region were determined. A possible polyadenylation signal was identified. Transcriptional regulation was investigated by transient transfections using various promoter fragments. A -1100 sst2 promoter directed significant levels of luciferase expression in GH4 rat pituitary cells and Skut1-B endometrium cells whereas only low activity was detected in JEG3 chorion carcinoma cells or COS-7 monkey kidney cells. A minimal -252 promoter allowed cell specific expression. We did not find any regulation of the sst2 promoter by somatostatin, forskolin, TRH, TPA, T3, and 17beta-estradiol. Glucocorticoids lead to a significant inhibition of sst2 promoter activity. Further mapping suggest a glucocorticoid-responsive element between -905 and -707 and between -252 and -163. These studies demonstrate the nature of the human sst2 gene and identify its 5' and 3' flanking regions. Furthermore, specific activity of the promoter and regulation by various hormones is demonstrated.
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PMID:Genomic structure and transcriptional regulation of the human somatostatin receptor type 2. 1061 99

Synthetic GH secretagogues stimulate GH release through binding to a recently cloned specific GH secretagogue receptor (GHS-R). The endogenous ligand of this receptor may be part of a new endocrine pathway controlling GH secretion. Two different receptor variants, type 1a and 1b, have been described that differ in their 3'-terminal amino acids. We investigated the genomic structure and transcriptional regulation of the human GHS-R. An 18-kb genomic clone including sequences encoding for the two GHS-R variants was isolated. Sequencing revealed that the two variants originate from specific RNA processing of a single gene that spans approximately 4.1 kb. The transcription start site was defined by 5'-inverse PCR analysis at position -227. RT-PCR analysis points to differential transcriptional initiation and processing. Type 1a is encoded by two exons; 2152 bp of intronic sequence are removed by splicing at position 796/797 relative to the translation start site. Type 1b is encoded by a single exon. A putative polyadenylation signal consensus motif was identified at position +4118; 2.7 kb of the 5'-flanking region were sequenced, and putative transcription factor binding sites were identified. Transcriptional regulation was investigated by transient transfections using promoter fragments ranging in size from 168-1745 bp; 1745 bp of the GHS-R promoter directed significant levels of luciferase expression in GH(4) rat pituitary cells, whereas no activity was detected in monkey kidney COS-7 cells, human endometrium Skut-1B cells, mouse hypothalamic LHRH neuronal GT1-7 cells, or mouse corticotroph pituitary AtT20 cells. A minimal 309-bp promoter allowed pituitary-specific expression. Its activity in COS-7 cells was enhanced by cotransfection of the pituitary-specific transcription factor Pit-1. We did not find any regulation of the GHS-R promoter by forskolin, somatostatin, insulin-like growth factor I, or 12-O-tetraphorbol 12-myristate 13-acetate. Thyroid hormone and estrogen lead to a significant stimulation; glucocorticoids lead to a significant inhibition. Further mapping suggests a thyroid hormone-responsive element, an estrogen-responsive element, and a glucocorticoid-responsive element located between -309 and the translation start codon. These studies demonstrate the nature of the human GHS-R gene and identify its 5'-flanking region. Furthermore, pituitary-specific activity of the promoter and regulation by various hormones are demonstrated.
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PMID:Genomic structure and transcriptional regulation of the human growth hormone secretagogue receptor. 1135 16

Somatostatin (SRIF) exerts inhibitory effects on virtually all endocrine and exocrine secretions. Five distinct SRIF receptor subtypes (sst 1-5) have been identified. In contrast to the other subtypes, very little is known about specific functions of sst4. We investigated structure and regulation of the human sst4 gene. A genomic clone containing the 5' region of the sst4 gene was isolated. 1.5 kb of the promoter was sequenced and putative transcription factor binding sites were identified. The transcription start site was located 88 nucleotides upstream of the translation start site. A -984 sst4 promoter directed significant levels of luciferase expression in GH4 rat pituitary cells, Skut-1B endometrium cells, and BEAS-2B human bronchial epithelial cells, whereas only low activity was detected in JEG3 chorion carcinoma cells or COS-7 monkey kidney cells. A minimal -209 promoter allowed cell specific expression, its activity in COS-7 cells is not enhanced by co-transfection of the pituitary-specific transcription factor Pit-1. An enhancer element was localized between nt -459 and -984. We did not find any regulation of the sst4 promoter region analyzed by SRIF, forskolin, TPA, IGF-1, EGF, T3, glucocorticoids or 17beta-estradiol. These studies identify the 5' region of the sst4 gene. Furthermore, specific activity of the promoter in various cell lines is demonstrated.
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PMID:Characterization of the human somatostatin receptor type 4 promoter. 1191 48

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.
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PMID:Characterization and transcriptional regulation of the human somatostatin receptor subtype 1 gene. 1753 78

In the present paper the effects of 17beta-estradiol on the expression of the preprosomatostatin 1 (PSS1) in the orange-spotted grouper hypothalamus and ovary were investigated. Results from in vivo of intraperitoneal injection and in vitro static cultures showed that estradiol increased the mRNA expression of PSS1 gene in both hypothalamus and ovary. To investigate the molecular basis of the estrogen regulation on PSS1 gene expression, we cloned the upstream region of 848bp from the translation initiation codon of the grouper PSS1 gene. The TATA-box and putative transcription factor binding sites were identified using computer analysis. Transient transfections with promoter-luciferase reporter constructs together with hER expression vector were carried out in MCF-7 cell line. The results suggest that the region from -848 to -373bp, containing five putative ERE half sites, may contribute to the promoter activity induced by estradiol. These results represent the first demonstration at the molecular level of the regulation of PSS1 gene by 17beta-estradiol in fish.
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PMID:Regulation of preprosomatostatin 1 (PSS1) gene expression by 17beta-estradiol and identification of the PSS1 promoter region in orange-spotted grouper (Epinephelus coioides). 1955 50