The POU Domain Transcription Factor Tst-1 Activates Somatostatin Receptor 1 Gene Expression in Pancreatic β-Cells

Abstract

The major neuroendocrine cell types of pancreatic islets, the ␣-, ␤-, ␦-, and pancreatic polypeptide-cells, secrete the peptide hormones, glucagon, insulin, somatostatin, and pancreatic polypeptide, respectively. These hormones are powerful regulators of whole body metabolism and are released in response to gastrointestinal, nutritional, and neuronal signals (1). One important function of somatostatin is to limit the secretion of insulin, glucagon, pancreatic polypeptide, and somatostatin itself (1, 2). Molecular cloning identified six somatostatin receptors (sst1, sst2A, sst2B, sst3, sst4, and sst5) that bind somatostatin with high affinity, are coupled to G-proteins, and regulate various cellular effectors (for review see Refs. 3 and 4). The sst subtypes are encoded by five genes that are differentially expressed in human and rat pancreatic islets. sst1 has been exclusively detected in human ␤-cells, whereas sst2 is confined to ␣-cells. sst3 and sst4 were found in subpopulations of ␤-cells. sst5 is present in ␤-and ␦-cells (5). Similar results were obtained in rat pancreatic islets for sst2A and sst5 (6). In line with these observations sst2-and sst5-specific agonists inhibited the release of glucagon and insulin from rodent islet preparations, respectively (7-10). An sst1-specific agonist, [des-Ala

Expression efficiency of <i>NAT2</i> haplotypes in a Korean population

“…According to previous reports, TST-1 is a trans-activator which mediates 5′-TTAATCATT-3′ motif-dependent transcription. It has also been demonstrated that TST-1 acts as a transcriptional regulator in pancreatic β-cells (Baumeister and Meyerhof, 2000). However, we failed to find a significant relationship between rs4646241 and enzyme expression level.…”

Regulation and function of somatostatin receptors

“…pancreatic b-cells, the proximal Pit-1 binding site is specifically bound by the transcription factors Oct-1 and Tst-1, another POU domain protein, which is expressed in islet b-cells (Baumeister and Meyerhof 2000b). From these data, it appears that this proximal promoter element functions as a binding site for tissue-specific-expressed POU domain proteins and thereby guides sst1 gene expression in neuroendocrine cells.…”

“…Taken together, an attractive concept for genetic control arises in the anterior pituitary in which the genes for the hypophysiotropic hormones, PRL, thyroid‐stimulating hormone (TSH)‐β and GH as well as the genes for receptors that regulate their secretion, growth hormone releasing hormone receptor (GHRH‐R; Andersen and Rosenfeld 1994) and sst1 are commonly controlled by the same pituitary‐specific transcription factor Pit‐1. In pancreatic β‐cells, the proximal Pit‐1 binding site is specifically bound by the transcription factors Oct‐1 and Tst‐1, another POU domain protein, which is expressed in islet β‐cells (Baumeister and Meyerhof 2000b). From these data, it appears that this proximal promoter element functions as a binding site for tissue‐specific‐expressed POU domain proteins and thereby guides sst1 gene expression in neuroendocrine cells.…”

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

“…Sequence analyses of the rat Sstr1 gene promoter ( Baumeister and Meyerhof, 1998 , 2000a ) demonstrated presence of putative transcription factor binding sites [GC box transcription factor, specificity protein 1, and activator protein (AP)-2] that are often found in TATA-less promoters ( Smale et al, 1990 ). Presence of binding sites for tissue-specific transcriptional factors of the POU domain protein family ( Rosenfeld, 1991 ) was also noted, including sites for pituitary-specific positive transcription factor 1 and POU family transcription factor Tst-1 that regulate tissue-specific rat Sstr1 gene expression in the pituitary and in pancreatic β -cells, respectively ( Baumeister and Meyerhof, 1998 , 2000b ). The porcine Sstr1 gene promoter showed positive regulation by cAMP (through a CREBBP1 binding site) ( Gahete et al, 2014 ), consistent with the cAMP-mediated upregulation of SST 1 mRNA in rat pituitary primary cultures induced by GHRH treatment ( Park et al, 2000 ), and in pituitary adenomas expressing a mutated G α s (gsp oncogene) that constitutively activates the cAMP pathway ( Kim et al, 2005 ).…”