Somatostatin (SST) peptide forms and receptor subtypes correlate with aging-related CNS and GI diseases

The tetradecapeptide somatostatin (SST), initially known for inhibiting growth hormone (GH) secretion, plays broader roles beyond the hypothalamic–pituitary–somatotropic (HPS) axis. Dysregulation of SST and its signaling pathways is implicated in various age-related pathologies, particularly within the central nervous system (CNS) and gastrointestinal (GI) tract. Understanding the specific forms and receptor interactions of SST is crucial for identifying therapeutic targets in these complex diseases, where current treatments often lack specificity or efficacy.

This paper serves as an introductory overview to a review, synthesizing existing literature on the peptide somatostatin (SST). It describes the peptide's discovery, gene structure, and biologically active forms (SST-14 and SST-28). The review also details the interaction of SST and cortistatin (CST) with five G protein-coupled receptor (GPCR) subtypes, SST1-5 (SSTRs), across various mammalian organs, including the brain and GI tract. The authors lay the groundwork for exploring SST's correlations with selected CNS and GI tract diseases in aging.

Somatostatin (SST) was first identified as a 14 amino acid (AA) peptide that inhibited GH secretion at 1 × 10−9 M in vitro and in vivo. The human SST gene, located on chromosome 3, has 1 transcript and 262 orthologues, with its expression regulated by methylation, polymorphisms, and transcription factors. SST occurs in two biologically active forms: SST-14 (secreted mainly by nerve cells and pancreatic islet δ cells) and SST-28 (the main product of D cells in the GI tract). Both forms are derived from a larger 120 AA precursor, preprosomatostatin. In the mammalian brain, the SST family includes SST and cortistatin (CST), which shares 11 AA with SST.