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Review
. 2020 Jun 11;21(11):4170.
doi: 10.3390/ijms21114170.

Regulatory Mechanisms of Somatostatin Expression

Emmanuel Ampofo  1 , Lisa Nalbach  1 , Michael D Menger  1 , Matthias W Laschke  1
Affiliations
Review

Regulatory Mechanisms of Somatostatin Expression

Emmanuel Ampofo et al. Int J Mol Sci. .

Abstract

Somatostatin is a peptide hormone, which most commonly is produced by endocrine cells and the central nervous system. In mammals, somatostatin originates from pre-prosomatostatin and is processed to a shorter form, i.e., somatostatin-14, and a longer form, i.e., somatostatin-28. The two peptides repress growth hormone secretion and are involved in the regulation of glucagon and insulin synthesis in the pancreas. In recent years, the processing and secretion of somatostatin have been studied intensively. However, little attention has been paid to the regulatory mechanisms that control its expression. This review provides an up-to-date overview of these mechanisms. In particular, it focuses on the role of enhancers and silencers within the promoter region as well as on the binding of modulatory transcription factors to these elements. Moreover, it addresses extracellular factors, which trigger key signaling pathways, leading to an enhanced somatostatin expression in health and disease.

Keywords: brain-derived neurotrophic factor (BDNF); cAMP resonse element (CRE); central nervous system (CNS); glutamateric system; growth hormone (GH); gut; hypothalamus; paired box protein (PAX)6; pancreas; pancreas/duodenum homeobox protein (PDX)1; pre-prosomatostatin; somatostatin; δ-cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Genomic regions for the human somatostatin gene and the orthologue genes in rats and mice. Human somatostatin is located on chromosome 3, whereas mouse somatostatin is located on chromosome 11 and rat somatostatin on chromosome 16. Genomic contexts are conserved in the three species regarding the receptor transporter protein (RTP)2.
Figure 2
Figure 2
Regulatory elements of the rat somatostatin promoter. The somatostatin promoter harbors a complex arrangement of multiple regulatory elements, such as cAMP response element (CRE), specific upstream-enhancer elements (SMS-UE, SMS-TAAT1, and SMS-TAAT2) interspersed with the proximal silencer elements (SMS-PS1 and SMS-PS2) upstream of the TATA box. Moreover, additional methylation sites, i.e., GpC islets and poly-T repeats, are found in the somatostatin promoter region.
Figure 3
Figure 3
The regulatory mechanisms of somatostatin expression. It is known that the cellular somatostatin content is pretranslationally regulated by methylations and polymorphisms within the promoter region as well as by the activity of different transcription factors (green arrows). On the posttranslational level, the cellular somatostatin content is regulated by proteolytic cleavage of pre-prosomatostatin into somatostatin (SS-14 and SS-28) and by secretion (green arrows). Further putative factors and mechanisms, which may regulate the expression of the peptide hormone, are miRNAs, alternative splicing, autocrine feedback, and protein modification (yellow arrows).
See this image and copyright information in PMC

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