Somatostatin (SS) is a polypeptide hormone with numerous inhibitory roles in the body. It was initially identified as a product of hypothalamic neurones but has been found to be produced in the GI tract, and exerts many of its key effects there.
Due to its effect on growth hormone, it is also referred to as growth hormone inhibiting hormone.
This article will examine the structure of somatostatin its function on the body and its clinical relevance.
Structure
SS is a polypeptide hormone capable of inhibiting the actions of various pancreatic and gastrointestinal hormones.
SS has a high binding affinity to five different SS receptors in the G protein-coupled receptor superfamily. These receptors are coupled to inhibitory G proteins and are involved in motility, mucous and hormone secretion and inflammatory responses.
Effects of Somatostatin – Gastrointestinal System
Production
SS is produced by in the D cells of the stomach and duodenum, and the δ cells of the islets of Langerhans of the pancreas. SS secretion is stimulated by the presence of glucose, amino acids and glucagon-like peptide-1.
SS has numerous regulatory functions in the gastrointestinal system. Its primary role in gastric physiology is to inhibit both gastrin release and parietal cell acid secretion.
Effect on Gastric Acid Secretion
Somatostatin inhibits gastric acid secretion via an indirect and a direct pathway.
Direct Pathway
Depending on the source of the SS, the hormone can act in a paracrine or an endocrine fashion.
In the stomach, D cells are found near the base of the oxyntic glands, the predominant gland type within the body and fundus of the stomach. When released into the stomach, SS binds to a alpha-1 G-protein coupled receptor on the basolateral membrane of the parietal cell.
This binding leads to the inhibition of adenylyl cyclase, antagonising the stimulatory effect of histamine, and thus inhibiting gastric acid secretion by parietal cells.
Indirect Pathway
SS can activate two indirect paracrine pathways on G and D cells of the stomach.
Histamine and gastrin are both examples of secretagogues which are substances that cause another substance to be secreted and due to this function, SS can inhibit gastric acid secretion.
In the corpus of the stomach, D cells release the hormone to inhibit the release of histamine from the Enterochromaffin-like cells (ECL cells).
In the antrum of the stomach, the release of SS from the D cells inhibits the release of gastrin from G cells. This is an example of redundant regulatory pathways that control acid secretion.
Effects in the Pancreas
In the pancreas, SS is secreted by δ-cells (delta cells). Once released, it acts as a powerful inhibitor of glucagon and insulin secretion from the α- and β-cells, respectively.
Glucose stimulates SS secretion via G-proteins. When blood glucose concentrations are high, activation of cellular receptors causes the closure of ATP-sensitive K+ channels, initiating membrane depolarisation and increasing SS release from delta cells. This is comparable to the mechanism of insulin secretion.
It also suppresses pancreatic exocrine secretions through the inhibition of cholecystokinin-stimulated enzyme secretion and secretin-stimulated bicarbonate secretion.
Summary list of Gastrointestinal Effects
Below is a list of the effects of somatostatin in the GI tract. The mechanisms of all of the actions listed below is beyond the scope of this article:
Effects of Somatostatin – Nervous System
SS is produced in the brain as well as the gastrointestinal tract.
A key producer of this neuropeptide is the hypothalamus, which predominantly synthesises the 14 amino acid form of the hormone in the periventricular region. SS-14 is released into the hypophyseal portal blood system.
SS is a potent Growth Hormone (GH) inhibitor, thus is sometimes referred to as Growth Hormone Inhibiting Hormone (GHIH). Whilst many hypothalamic-pituitary axes are controlled through a negative feedback mechanism, control of GH is regulated through both positive and negative control.
Summary of Neurological Effects
- Inhibits secretion of growth hormone from the anterior pituitary
- Inhibits secretion of thyroid-stimulating hormone from the anterior pituitary
Clinical Relevance
Synthetic Somatostatin
As SS inhibits the secretion of multiple hormones, this property has led to the production of long-acting SS analogues, such as octreotide for the treatment of some endocrine tumours. Octreotide can be used to treat tumours that produce GH (acromegaly), insulin (insulinoma), or serotonin (carcinoid tumours). Common side effects of SS analogues include gastrointestinal upset, cholelithiasis and impaired glucose tolerance. SS antagonists have also been used to correct impaired glucagon secretion in response to hypoglycaemia in diabetes mellitus.
Glucose Tolerance Test
Acromegaly is a condition in which there is excess circulating growth hormone. This leads to a variety of signs and symptoms including altered facial appearance, increased hand/foot size, cardiomyopathy, carpal tunnel syndrome and patchy skin changes known as acanthosis nigricans.
One method of testing for acromegaly is to undertake a glucose tolerance test. The participant is given a high dose of glucose, which under normal conditions should lead to inhibition of growth hormone through the release of somatostatin.
In patients with excessive/dysregulated growth hormone, serum levels of growth hormone will remain excessive despite the inhibitory action of somatostatin. This points towards a diagnosis of acromegaly.