What are the types, actions, and regulators of Somatostatin (SST)?

From the Guidelines

Somatostatin is a peptide hormone that exists in two main types: somatostatin-14 and somatostatin-28, and its primary actions include inhibition of hormone release, suppression of cell proliferation, and reduction of digestive enzyme secretion, as supported by the most recent study 1.

Types and Actions of Somatostatin

Somatostatin acts primarily as an inhibitory hormone throughout the body, with its main actions including:

• Inhibition of growth hormone and thyroid-stimulating hormone release from the pituitary gland
• Suppression of insulin and glucagon secretion from the pancreas
• Reduction of gastric acid production
• Slowing of gastric emptying and intestinal motility
• Inhibition of various digestive enzymes It also reduces blood flow to the intestines and inhibits the release of other gastrointestinal hormones like gastrin, cholecystokinin, and secretin.

Regulators of Somatostatin

Somatostatin release is regulated by several factors, including:

• High blood glucose levels
• Amino acids (particularly arginine and alanine)
• Fatty acids
• Various hormones including growth hormone, glucagon, and insulin Inhibitory regulators include insulin-like growth factor-1 (IGF-1) and low blood glucose levels.

Somatostatin Signaling and Clinical Use

Somatostatin signaling occurs through binding to five different G protein-coupled receptors (SSTR1-5), which are distributed differently throughout tissues, explaining its diverse physiological effects. Synthetic analogs like octreotide and lanreotide are used clinically to treat conditions involving hormone hypersecretion, such as acromegaly and certain neuroendocrine tumors, as recommended by the most recent guidelines 1. The use of somatostatin analogs, such as lanreotide, is recommended for tumor growth control in advanced SSTR-positive, slowly-growing GI and Pan-NETs up to a Ki-67 of 10% 1.

From the FDA Drug Label

The mechanism of action of lanreotide is believed to be similar to that of natural somatostatin. Lanreotide has a high affinity for human somatostatin receptors (SSTR) 2 and 5 and a reduced binding affinity for human SSTR1, 3, and 4. Like somatostatin, lanreotide is an inhibitor of various endocrine, neuroendocrine, exocrine, and paracrine functions The primary pharmacodynamic effect of lanreotide is a reduction of GH and/or IGF-1 levels enabling normalization of levels in acromegalic patients

Types of Somatostatin:

• Natural somatostatin
• Lanreotide, an octapeptide analog of natural somatostatin

Actions of Somatostatin:

• Inhibitor of various endocrine, neuroendocrine, exocrine, and paracrine functions
• Reduction of GH and/or IGF-1 levels
• Inhibition of basal secretion of motilin, gastric inhibitory peptide, and pancreatic polypeptide
• Inhibition of postprandial secretion of pancreatic polypeptide, gastrin, and cholecystokinin (CCK)
• Reduction and delay in postprandial insulin secretion
• Inhibition of meal-stimulated pancreatic secretions
• Reduction of duodenal bicarbonate and amylase concentrations
• Transient reduction in gastric acidity
• Inhibition of gallbladder contractility and bile secretion

Regulators of Somatostatin:

• Somatostatin receptors (SSTR) 1,2,3,4, and 5, with high affinity for SSTR 2 and 5 2

From the Research

Types of Somatostatin

• Somatostatin-14: a shorter form of somatostatin, involved in the regulation of glucagon and insulin synthesis in the pancreas 3
• Somatostatin-28: a longer form of somatostatin, involved in the regulation of glucagon and insulin synthesis in the pancreas 3
• Octreotide: a synthetic biologically stable somatostatin analogue, used in the treatment of acromegaly and gastroenteropancreatic neuroendocrine tumours (GEP-NET) 4, 5
• Lanreotide: another somatostatin analogue, used in the treatment of acromegaly and GEP-NET 4, 6
• Pasireotide: a next-generation multireceptor-targeted somatostatin analogue, used in the treatment of acromegaly 4

Actions of Somatostatin

• Inhibits the release of anterior pituitary growth hormone and thyroid-stimulating hormone 5, 7
• Inhibits the release of peptides of the gastroenteropancreatic endocrine system 5, 7
• Regulates the secretion of hormones such as growth hormone and thyroid-stimulating hormone in healthy and pathological states 6
• Involved in the regulation of glucagon and insulin synthesis in the pancreas 3

Regulators of Somatostatin

• Enhancers and silencers within the promoter region of the somatostatin gene 3
• Modulatory transcription factors that bind to the promoter region of the somatostatin gene 3
• Extracellular factors that trigger key signaling pathways, leading to an enhanced somatostatin expression in health and disease 3