Sst, short for somatostatin, is a cyclic peptide that plays a crucial role in multiple biological processes. It inhibits the release of hormones and neurotransmitters by binding to one of five canonical G protein-coupled SST receptors (SSTR1-SSTR5) [5,6]. Sst is involved in regulating cell proliferation, and its associated pathways, such as the GH-IGF-SST system, are important in liver growth, development, and hepatocarcinogenesis [4]. Genetically modified mouse models, like Sst-Cre mice, are valuable tools for studying Sst-related functions [3].

In mice, excitatory somatostatin-positive neurons (MPLSST neurons) in the medial paralemniscal nucleus promote self-grooming and encode reward. Loss of function of MPLSST neurons impairs self-grooming and post-stress anxiety alleviation, revealing the role of Sst-expressing neurons in these behaviors [1]. In small intestinal neuroendocrine tumors (SI-NETs), SST2 expression, related to Sst, is regulated by DNA methylation, as SI-NETs have lower SST2 promoter methylation levels compared to normal tissue, and SST2 mRNA expression negatively correlates with DNA methylation [2].

In conclusion, Sst is essential for regulating hormone release, cell proliferation, and is involved in behaviors like self-grooming and anxiety regulation in mice. The use of Sst-related mouse models has provided insights into its role in these processes. In addition, understanding the epigenetic regulation of Sst-related receptors in tumors like SI-NETs can potentially contribute to better diagnosis and treatment strategies for such diseases.

References:

1. Sun, Jingjing, Yuan, Yuan, Wu, Xiaohua, Xu, Tian-Le, Huang, Ju. 2022. Excitatory SST neurons in the medial paralemniscal nucleus control repetitive self-grooming and encode reward. In Neuron, 110, 3356-3373.e8. doi:10.1016/j.neuron.2022.08.010. https://pubmed.ncbi.nlm.nih.gov/36070748/

2. Klomp, Maria J, Refardt, Julie, van Koetsveld, Peter M, Hofland, Johannes, Hofland, Leo J. 2023. Epigenetic regulation of SST2 expression in small intestinal neuroendocrine tumors. In Frontiers in endocrinology, 14, 1184436. doi:10.3389/fendo.2023.1184436. https://pubmed.ncbi.nlm.nih.gov/37223009/

3. Foss, Calvin T, Olsen, Timothy, Bigelow, James, Hasenstaub, Andrea R. 2024. Sst- and Vip-Cre mouse lines without age-related hearing loss. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.07.15.603003. https://pubmed.ncbi.nlm.nih.gov/39071442/

4. Pivonello, Claudia, De Martino, Maria Cristina, Negri, Mariarosaria, Colao, Annamaria, Pivonello, Rosario. 2014. The GH-IGF-SST system in hepatocellular carcinoma: biological and molecular pathogenetic mechanisms and therapeutic targets. In Infectious agents and cancer, 9, 27. doi:10.1186/1750-9378-9-27. https://pubmed.ncbi.nlm.nih.gov/25225571/

5. Solarski, Michael, Williams, Declan, Mehrabian, Mohadeseh, Wille, Holger, Schmitt-Ulms, Gerold. 2019. The human brain somatostatin interactome: SST binds selectively to P-type family ATPases. In PloS one, 14, e0217392. doi:10.1371/journal.pone.0217392. https://pubmed.ncbi.nlm.nih.gov/31136617/

6. Sun, Lichun, Coy, David H. . Somatostatin and its Analogs. In Current drug targets, 17, 529-37. doi:. https://pubmed.ncbi.nlm.nih.gov/26951062/