Somatostatin (SST) is a small peptide that functions as both a hormone and a neurotransmitter throughout the body. It is recognized primarily for its inhibitory nature, acting as a broad-spectrum “off-switch” for various biological processes. SST helps maintain physiological balance by suppressing the release of numerous hormones, slowing digestion, and regulating cell growth. It exists in two main active forms, composed of either 14 (SST-14) or 28 (SST-28) amino acids, derived from a larger precursor protein. The name, meaning “stagnation of a body,” reflects its fundamental role in dampening secretory and proliferative activities across multiple organ systems.
Synthesis and Distribution Across Body Systems
Somatostatin is produced across several body systems, reflecting its wide-ranging regulatory functions. It is synthesized from a precursor protein, preprosomatostatin, and processed into the active forms, SST-14 and SST-28. SST-14 is more common in the central nervous system, while SST-28 is prevalent in the gut.
A prominent site of production is the hypothalamus, where SST is released as a neurohormone to regulate the pituitary gland’s output. In the pancreas, SST is synthesized by the delta cells (δ-cells) within the Islets of Langerhans, interspersed among insulin and glucagon-producing cells. This strategic location allows it to act locally on neighboring cells in a paracrine fashion.
The gastrointestinal (GI) tract is another major source, where specialized endocrine D cells produce SST throughout the stomach and intestines. In the GI system, somatostatin acts locally to control digestive processes and also enters the bloodstream as a circulating hormone. Approximately 65% of circulating SST originates from the GI tract, 30% from the central nervous system, and 5% from the pancreas.
The Primary Role as a Universal Inhibitor
Somatostatin acts as a universal inhibitor by binding to a family of five different G protein-coupled somatostatin receptors (SSTR1 through SSTR5) found on target cells. Upon activation, these receptors typically inhibit the production of a signaling molecule called cyclic AMP (cAMP), effectively shutting down the cell’s secretory machinery. This inhibitory action is essential for maintaining metabolic and hormonal homeostasis across the endocrine and digestive systems.
Regulation of the Endocrine System
In the brain and pituitary gland, somatostatin controls the body’s growth axis. It is a suppressor of Growth Hormone (GH) release from the anterior pituitary gland, which is why it is sometimes referred to as Growth Hormone Inhibitory Hormone (GHIH). By controlling GH secretion, somatostatin indirectly manages the production of Insulin-like Growth Factor 1 (IGF-1) from the liver. It also suppresses the release of Thyroid-Stimulating Hormone (TSH), regulating the thyroid gland’s function.
Pancreatic and Metabolic Control
Within the pancreas, somatostatin exerts its paracrine control to finely tune blood sugar levels. Released from the delta cells, it rapidly inhibits the secretion of both insulin from the beta cells and glucagon from the alpha cells. This dual inhibitory action prevents excessive fluctuations in blood glucose following a meal. SST also suppresses the exocrine function of the pancreas, reducing the secretion of digestive enzymes and bicarbonate into the small intestine.
Gastrointestinal Inhibition
The gastrointestinal tract is extensively regulated by somatostatin, which acts to slow down the entire digestive process. It achieves this by suppressing the release of a wide variety of gut hormones, including gastrin, secretin, and cholecystokinin. The inhibition of gastrin leads to a reduction in gastric acid secretion by the parietal cells in the stomach. Furthermore, SST reduces intestinal motility and decreases blood flow to the digestive organs, collectively promoting a pause in digestion and absorption.
Clinical Applications: Somatostatin Analogs
The short half-life of natural somatostatin, which is only about one to three minutes, makes it impractical for therapeutic use in its native form. To overcome this limitation, synthetic compounds known as somatostatin analogs (SSAs), such as Octreotide and Lanreotide, were developed. These analogs mimic the inhibitory effects of natural SST but have a much longer duration of action, often lasting for weeks when administered in long-acting formulations.
The development of these analogs was made possible because many cells, particularly tumor cells, overexpress somatostatin receptors, especially the SSTR2 subtype. Synthetic analogs are engineered to have a high affinity for these receptors, which allows for targeted therapeutic effects. The extended half-life permits convenient dosing, typically once per month.
Treatment of Acromegaly
Somatostatin analogs are used to treat acromegaly, a disorder caused by the excessive secretion of Growth Hormone (GH) from a pituitary tumor. By binding to SSTRs on the tumor cells, the analogs suppress GH release, normalizing high levels of IGF-1. This treatment controls hormonal hypersecretion and can also lead to a measurable reduction in the size of the pituitary tumor in a significant number of patients.
Management of Neuroendocrine Tumors (NETs)
SSAs are integral to the management of Neuroendocrine Tumors (NETs), a group of cancers that often arise in the pancreas or gastrointestinal tract. These tumors frequently secrete excessive amounts of hormones, leading to debilitating conditions like carcinoid syndrome, characterized by severe diarrhea and flushing. The analogs effectively control these symptoms by inhibiting the hypersecretion of the tumor-derived hormones. Beyond symptom control, SSAs also demonstrate an anti-proliferative effect, slowing the growth and progression of well-differentiated NETs.
Diagnostic Imaging
The high affinity of these analogs for SSTRs is also utilized in diagnostic imaging, such as the Octreoscan. This technique involves attaching a radioactive tracer to the somatostatin analog, which is then injected into the patient. The tracer binds specifically to the somatostatin receptors present on NET cells, allowing medical imaging to precisely locate the tumors and any metastatic spread throughout the body.