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Horm Metab Res 2007; 39(5): 359-365
DOI: 10.1055/s-2007-976540
Original Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Characterization and Transcriptional Regulation of the Human Somatostatin Receptor Subtype 1 Gene

A. Redmann 1 , A. Rasch 2 , H. Tourné 1 , K. Mann 1 , S. Petersenn 1
  • 1Division of Endocrinology, Medical Center, University of Essen, Essen, Germany
  • 2IHF, Institute for Hormone and Fertility Research, University of Hamburg, Hamburg, Germany
Further Information

Publication History

received 17. 7. 2006

accepted 22. 12. 2006

Publication Date:
29 May 2007 (online)

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Abstract

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.

Key words

somatostatin receptor - G-protein coupled receptor - structure - regulation

References

  • 1 Badway AC, Blake AD. Somatostatin: a hormone for the heart?.  Curr Vasc Pharmacol. 2005;  3 125-131
    CrossrefPubMedGoogle Scholar
  • 2 Hofland LJ, Lamberts SW. Somatostatin receptors in pituitary function, diagnosis and therapy.  Front Horm Res. 2004;  32 235-252
    PubMedGoogle Scholar
  • 3 Reichlin S. Somatostatin.  N Engl J Med. 1983;  309 1495-1501
    CrossrefPubMedGoogle Scholar
  • 4 Reubi JC, Laissue JA. Multiple actions of somatostatin in neoplastic disease.  Trends Pharmacol Sci. 1995;  16 110-115
    CrossrefPubMedGoogle Scholar
  • 5 Ballian N, Brunicardi FC, Wang XP. Somatostatin and its receptors in the development of the endocrine pancreas.  Pancreas. 2006;  33 1-12
    CrossrefPubMedGoogle Scholar
  • 6 Gillies G. Somatostatin: the neuroendocrine story.  Trends Pharmacol Sci. 1997;  18 87-95
    CrossrefPubMedGoogle Scholar
  • 7 Meyerhof W. The elucidation of somatostatin receptor functions: a current view.  Rev Physiol Biochem Pharmacol. 1998;  133 55-108
    PubMedGoogle Scholar
  • 8 Reisine T, Bell GI. Molecular biology of somatostatin receptors.  Endocr Rev. 1995;  16 427-442
    CrossrefPubMedGoogle Scholar
  • 9 Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile.  Eur J Endocrinol. 2002;  146 707-716
    Google Scholar
  • 10 Thermos K, Bagnoli P, Epelbaum J, Hoyer D. The somatostatin sst1 receptor: an autoreceptor for somatostatin in brain and retina?.  Pharmacol Ther. 2006;  110 455-464
    CrossrefPubMedGoogle Scholar
  • 11 Lahlou H, Guillermet J, Hortala M. et al . Molecular signaling of somatostatin receptors.  Ann N Y Acad Sci. 2004;  1014 121-131
    CrossrefPubMedGoogle Scholar
  • 12 Sharma K, Patel YC, Srikant CB. Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3.  Mol Endocrinol. 1996;  10 1688-1696
    CrossrefPubMedGoogle Scholar
  • 13 Helyes Z, Pinter E, Nemeth J. et al . Effects of the somatostatin receptor subtype 4 selective agonist J-2156 on sensory neuropeptide release and inflammatory reactions in rodents.  Br J Pharmacol. 2006;  149 405-415
    CrossrefPubMedGoogle Scholar
  • 14 Dal Monte M, Petrucci C, Vasilaki A. et al . Genetic deletion of somatostatin receptor 1 alters somatostatinergic transmission in the mouse retina.  Neuropharmacology. 2003;  45 1080-1092
    CrossrefPubMedGoogle Scholar
  • 15 Cammalleri M, Cervia D, Langenegger D. et al . Somatostatin receptors differentially affect spontaneous epileptiform activity in mouse hippocampal slices.  Eur J Neurosci. 2004;  20 2711-2721
    CrossrefPubMedGoogle Scholar
  • 16 Shen LP, Pictet RL, Rutter WJ. Human somatostatin I: sequence of the cDNA.  Proc Natl Acad Sci USA. 1982;  79 4575-4579
    CrossrefPubMedGoogle Scholar
  • 17 Hauser F, Meyerhof W, Wulfsen I, Schonrock C, Richter D. Sequence analysis of the promoter region of the rat somatostatin receptor subtype 1 gene.  FEBS Lett. 1994;  345 225-228
    CrossrefPubMedGoogle Scholar
  • 18 Debus N, Dutour A, Vuaroqueaux V, Oliver C, Ouafik L. The ovine somatostatin receptor subtype 1 (osst1): partial cloning and tissue distribution.  Domest Anim Endocrinol. 2001;  21 73-84
    CrossrefPubMedGoogle Scholar
  • 19 Lin X, Janovick JA, Brothers S, Conn PM, Peter RE. Molecular cloning and expression of two type one somatostatin receptors in goldfish brain.  Endocrinology. 1999;  140 5211-5219
    CrossrefPubMedGoogle Scholar
  • 20 Zeiner M, Gehring U. Cloning of 5′ cDNA regions by inverse PCR.  Biotechniques. 1994;  17 1050-1054
    PubMedGoogle Scholar
  • 21 Solovyev V, Salamov A. The Gene-Finder computer tools for analysis of human and model organisms genome sequences.  Proc Int Conf Intell Syst Mol Biol. 1997;  5 294-302
    PubMedGoogle Scholar
  • 22 Heinemeyer T, Wingender E, Reuter I. et al . Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL.  Nucleic Acids Res. 1998;  26 362-367
    CrossrefPubMedGoogle Scholar
  • 23 Milanesi L, D’Angelo D, Rogozin IB. GeneBuilder: interactive in silico prediction of gene structure.  Bioinformatics. 1999;  15 612-621
    CrossrefPubMedGoogle Scholar
  • 24 Panetta R, Greenwood MT, Warszynska A. et al . Molecular cloning, functional characterization, and chromosomal localization of a human somatostatin receptor (somatostatin receptor type 5) with preferential affinity for somatostatin-28.  Mol Pharmacol. 1994;  45 417-427
    PubMedGoogle Scholar
  • 25 Thoss VS, Perez J, Probst A, Hoyer D. Expression of five somatostatin receptor mRNAs in the human brain and pituitary.  Naunyn Schmiedebergs Arch Pharmacol. 1996;  354 411-419
    CrossrefPubMedGoogle Scholar
  • 26 Kumar U, Sasi R, Suresh S. et al . Subtype-selective expression of the five somatostatin receptors (hSSTR1-5) in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis.  Diabetes. 1999;  48 77-85
    CrossrefPubMedGoogle Scholar
  • 27 Patel YC. Somatostatin and its receptor family.  Front Neuroendocrinol. 1999;  20 157-198
    PubMedGoogle Scholar
  • 28 Smith WH, Nair RU, Adamson D. et al . Somatostatin receptor subtype expression in the human heart: differential expression by myocytes and fibroblasts.  J Endocrinol. 2005;  187 379-386
    CrossrefPubMedGoogle Scholar
  • 29 Petersenn S, Rasch AC, Bohnke C, Schulte HM. Identification of an upstream pituitary-active promoter of human somatostatin receptor subtype 5.  Endocrinology. 2002;  143 2626-2634
    CrossrefPubMedGoogle Scholar
  • 30 Glos M, Kreienkamp HJ, Hausmann H, Richter D. Characterization of the 5′-flanking promoter region of the rat somatostatin receptor subtype 3 gene.  FEBS Lett. 1998;  440 33-37
    CrossrefPubMedGoogle Scholar
  • 31 Gordon DF, Woodmansee WW, Lewis SR. et al . Cloning of the mouse somatostatin receptor subtype 5 gene: promoter structure and function.  Endocrinology. 1999;  140 5598-5608
    CrossrefPubMedGoogle Scholar
  • 32 Woodmansee WW, Mouser RL, Gordon DF. et al . Mutational analysis of the mouse somatostatin receptor type 5 gene promoter.  Endocrinology. 2002;  143 2268-2276
    CrossrefPubMedGoogle Scholar
  • 33 Petersenn S, Rasch AC, Presch S, Beil FU, Schulte HM. Characterization of the human somatostatin receptor type 4 promoter.  Mol Cell Endocrinol. 2002;  188 75-83
    CrossrefPubMedGoogle Scholar
  • 34 Kraus J, Woltje M, Schonwetter N, Hollt V. Gene structure and regulation of the somatostatin receptor type 2.  J Physiol Paris. 2000;  94 199-204
    PubMedGoogle Scholar
  • 35 Petersenn S, Rasch AC, Presch S, Beil FU, Schulte HM. Genomic structure and transcriptional regulation of the human somatostatin receptor type 2.  Mol Cell Endocrinol. 1999;  157 75-85
    CrossrefPubMedGoogle Scholar
  • 36 Schafer J, Baumeister H, Lorenz A, Meyerhof W. Localization of somatostatin receptor subtype mRNA in the rat gastrointestinal tract and regulation of SSTR1 gene expression.  Z Ernahrungswiss. 1998;  37 ((Suppl 1)) 75-79
    PubMedGoogle Scholar
  • 37 Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes.  J Mol Biol. 1987;  196 261-282
    CrossrefPubMedGoogle Scholar
  • 38 Cervia D, Nunn C, Fehlmann D. et al . Pharmacological characterisation of native somatostatin receptors in AtT-20 mouse tumour corticotrophs.  Br J Pharmacol. 2003;  139 109-121
    CrossrefPubMedGoogle Scholar
  • 39 Patel YC, Panetta R, Escher E, Greenwood M, Srikant CB. Expression of multiple somatostatin receptor genes in AtT-20 cells. Evidence for a novel somatostatin-28 selective receptor subtype.  J Biol Chem. 1994;  269 1506-1509
    PubMedGoogle Scholar
  • 40 Faisst S, Meyer S. Compilation of vertebrate-encoded transcription factors.  Nucleic Acids Res. 1992;  20 3-26
    CrossrefPubMedGoogle Scholar
  • 41 de la Hoya M, Vila V, Jimenez O, Castrillo JL. Anterior pituitary development and Pit-1/GHF-1 transcription factor.  Cell Mol Life Sci. 1998;  54 1059-1066
    CrossrefPubMedGoogle Scholar
  • 42 Baumeister H, Wegner M, Richter D, Meyerhof W. Dual regulation of somatostatin receptor subtype 1 gene expression by pit-1 in anterior pituitary GH3 cells.  Mol Endocrinol. 2000;  14 255-271
    CrossrefPubMedGoogle Scholar
  • 43 Sipos L, Gyurkovics H. Long-distance interactions between enhancers and promoters.  FEBS J. 2005;  272 3253-3259
    CrossrefPubMedGoogle Scholar
  • 44 Moore DD, Marks AR, Buckley DI. et al . The first intron of the human growth hormone gene contains a binding site for glucocorticoid receptor.  Proc Natl Acad Sci USA. 1985;  82 699-702
    CrossrefPubMedGoogle Scholar
  • 45 Bruno JF, Xu Y, Berelowitz M. Somatostatin regulates somatostatin receptor subtype mRNA expression in GH3 cells.  Biochem Biophys Res Commun. 1994;  202 1738-1743
    CrossrefPubMedGoogle Scholar
  • 46 Park S, Kamegai J, Johnson TA, Frohman LA, Kineman RD. Modulation of pituitary somatostatin receptor subtype (sst1-5) messenger ribonucleic acid levels by changes in the growth hormone axis.  Endocrinology. 2000;  141 3556-3563
    CrossrefPubMedGoogle Scholar
  • 47 Xu Y, Berelowitz M, Bruno JF. Dexamethasone regulates somatostatin receptor subtype messenger ribonucleic acid expression in rat pituitary GH4C1 cells.  Endocrinology. 1995;  136 5070-5075
    CrossrefPubMedGoogle Scholar
  • 48 James RA, Sarapura VD, Bruns C. et al . Thyroid hormone-induced expression of specific somatostatin receptor subtypes correlates with involution of the TtT-97 murine thyrotrope tumor.  Endocrinology. 1997;  138 719-724
    CrossrefPubMedGoogle Scholar
  • 49 Djordjijevic D, Zhang J, Priam M. et al . Effect of 17beta-estradiol on somatostatin receptor expression and inhibitory effects on growth hormone and prolactin release in rat pituitary cell cultures.  Endocrinology. 1998;  139 2272-2277
    CrossrefPubMedGoogle Scholar

Correspondence

PD Dr. med. S. Petersenn

Division of Endocrinology, Medical Center, University of Essen

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