Regulatory Mechanisms of Somatostatin Expression.

Emmanuel Ampofo,Lisa Nalbach,Michael D Menger,Matthias W Laschke

doi:10.3390/ijms21114170

Emmanuel Ampofo, Lisa Nalbach + Show 2 more

Open Access

https://doi.org/10.3390/ijms21114170

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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.

Highlights

Somatostatin, known as growth hormone-inhibiting hormone or somatotropin release-inhibiting factor, is a major product of the somatostatin gene [1]
It is known that SS-14 is expressed in the hypothalamus and in other parts of the central nervous system (CNS), in peripheral nerves and in pancreatic δ-cells [6]
Both SS-14 and SS-28 are stored in secretory granules and their secretion is regulated by dietary components, such as amino acids, glucose, and fat [9,10,11], as well as by the adrenergic and muscarinic systems [12,13]

Summary

Introduction

Somatostatin, known as growth hormone-inhibiting hormone or somatotropin release-inhibiting factor, is a major product of the somatostatin gene [1]. Neuronostatin is highly expressed in the spleen, pancreas, cerebrum, and hypothalamus [8] Both SS-14 and SS-28 are stored in secretory granules and their secretion is regulated by dietary components, such as amino acids, glucose, and fat [9,10,11], as well as by the adrenergic and muscarinic systems [12,13]. Both peptides exhibit a very short half-life (~1 min) in the circulation [14]. We provide an up-to-date overview of these mechanisms, taking into account the gene, promoter, and transcription factors, as well as important exogenous factors

The Somatostatin Gene

Transcription Factors Regulating Somatostatin Expression

Exogenous Factors Regulating Somatostatin Expression

Putative Autocrine Feedback

Conclusions