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Somatostatin

Also known as somatotropin release-inhibiting factor, SRIF, SST, somatostatin-14, somatostatin-28, GHIH

The body's own inhibitory brake on growth hormone release, and the template for octreotide and lanreotide.

clinically proven Growth hormone endogenous peptide

At a glance

Category
Growth hormone
Status
endogenous peptide
Made from
synthetic Chemically synthesised. The peptide was originally isolated from ovine (sheep) hypothalamic extracts in 1973, but the marketed preparation contains no animal material.
Route
Endogenous: paracrine and neuroendocrine release into the hypophyseal portal circulation and locally in gut, pancreas and brain. As a medicine: continuous intravenous infusion only
Half-life
1 to 2 minutes in blood, which is why the SmPC specifies continuous intravenous infusion and notes that stopping the infusion gives rapid remission of symptoms in overdose 5. Somatostatin-28 is longer-lived, at roughly 15 minutes. Degradation by ubiquitous peptidases is the single reason synthetic analogues had to be developed
Onset
seconds to minutes; the effect stops almost as soon as the infusion does
Molecular weight
1637.9 g/mol (somatostatin-14); approximately 3148 g/mol (somatostatin-28)
Sequence
Somatostatin-14: AGCKNFFWKTFTSC, cyclised by a disulfide bridge between the two cysteines (Cys3-Cys14). Somatostatin-28 is an N-terminally extended form containing the same 14-residue sequence at its C-terminus. Both derive from the 92-amino-acid preprosomatostatin precursor

A naturally occurring human hormone and neuropeptide, not a consumer product. Synthetic native somatostatin is marketed in some European countries as an intravenous product — the Belgian Somatostatine-Eumedica range (250 mcg, 3 mg and 6 mg), authorised for intestinal and pancreatic fistulae, for symptomatic treatment of hypersecretion by endocrine tumours of the digestive tract, and for acute oesophageal bleeding where endoscopic sclerotherapy cannot be applied because of the intensity of the bleeding 5. It is not FDA-approved in the United States, and its half-life of 1 to 2 minutes makes continuous intravenous infusion necessary; the SmPC states it is for hospital use and preferably in an intensive care unit 5. The clinically relevant products are the long-acting analogues octreotide, lanreotide and pasireotide.

Doping status: Not listed by WADA

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

Somatostatin was isolated from ovine hypothalamus by Brazeau, Guillemin and colleagues in 1973 and named for what it does: it inhibits the secretion of somatotropin, growth hormone 1. It exists in two bioactive forms, a 14-residue and a 28-residue peptide, both cyclised by a disulfide bridge, and both cleaved from the same precursor. The pharmacophore is a small stretch of the ring — Phe-Trp-Lys-Thr — and essentially every synthetic analogue is built around retaining that motif in a metabolically stable scaffold.

It acts through five G protein-coupled receptors, SSTR1 through SSTR5. Somatostatin-14 binds SSTR1-4 with high affinity, while somatostatin-28 is relatively more selective for SSTR5. All five couple to Gi/Go: they inhibit adenylyl cyclase and lower cAMP, activate inwardly rectifying potassium channels which hyperpolarise the cell, close voltage-gated calcium channels, and activate protein tyrosine phosphatases. The net effect on a secretory cell is that the calcium signal driving exocytosis is switched off.

In the growth hormone axis specifically, somatostatin is one half of a two-hormone control system. Hypothalamic GHRH neurons drive GH synthesis and release from pituitary somatotrophs; hypothalamic somatostatin neurons in the periventricular nucleus suppress it. The two are released out of phase with each other, and it is that alternation — GHRH high while somatostatin is low, then the reverse — that produces the characteristic pulsatile pattern of GH secretion rather than a steady trickle. On the somatotroph, SSTR2 and SSTR5 do most of the inhibitory work.

This is what makes somatostatin the gatekeeper for the whole category. A GHRH analogue such as sermorelin or tesamorelin can only produce a GH pulse during a trough in somatostatin tone; if somatostatin tone is high, the pituitary simply does not respond, which is why GHRH-analogue responses vary so much with time of day, sleep state, glucose and free fatty acid levels. Ghrelin receptor agonists (ipamorelin, hexarelin, the GHRPs, MK-677) partly circumvent this by suppressing hypothalamic somatostatin release in addition to acting directly on the somatotroph, which is the mechanistic basis for the well-documented synergy between a GHRH analogue and a GHRP given together. IGF-1 closes the loop from the periphery by stimulating hypothalamic somatostatin release, so raising IGF-1 by any route ultimately increases the brake.

Outside the GH axis somatostatin is broadly inhibitory: it suppresses TSH, insulin, glucagon, gastrin, secretin, cholecystokinin, vasoactive intestinal peptide and pancreatic exocrine secretion, slows gastric emptying and intestinal transit, reduces splanchnic blood flow, and acts as a neurotransmitter in cortex, hippocampus and amygdala. That breadth is why its analogues are used in acromegaly, neuroendocrine tumours and variceal bleeding — and equally why they cause gallstones and glucose disturbance.

What the research shows

Somatostatin's physiology is established beyond dispute — it is textbook endocrinology built on fifty years of work, and the Nobel Prize in Physiology or Medicine 1977 went in part to Guillemin for this line of research. Somatostatin as a therapeutic in its own right is a much smaller story: native somatostatin infusion has been studied mainly in acute gastrointestinal bleeding and pancreatic surgery, with mixed results, and has been largely superseded by its analogues and by other drug classes.

Research in humans

The physiological role in humans is well characterised through infusion studies: somatostatin infusion abolishes GH pulses, suppresses insulin and glucagon, and reduces splanchnic blood flow. As a treatment, continuous somatostatin infusion has been used in acute oesophageal variceal haemorrhage and to reduce output from pancreatic fistulae; the trial literature is old, heterogeneous, and in variceal bleeding it has been largely displaced by terlipressin and octreotide combined with endoscopic band ligation. There is no role for somatostatin itself as a chronic therapy, because the infusion requirement makes it impractical.

Animal and lab research

The original isolation was from ovine hypothalamic extracts, and the receptor subtypes were characterised largely in rodent pituitary and pancreatic islet preparations. Selective SSTR knockout and subtype-selective agonist work in rodents established that SSTR2 and SSTR5 mediate most of the inhibition of stimulated GH secretion from pituitary somatotrophs — the finding that directly justified designing octreotide and lanreotide as SSTR2-preferring agonists.

Caveats. The main limitation is practical rather than evidential: a 1-3 minute half-life makes native somatostatin useless as a therapy outside a hospital drip, and there is a rebound hypersecretion of GH and of gastric acid when an infusion is stopped abruptly. The therapeutic trial literature is largely pre-1995, small, and predates modern standards. Almost everything of current clinical relevance has been generated with the analogues rather than the native peptide.

What it is used for

  • Physiological: the endogenous inhibitor of growth hormone and TSH release from the pituitary, and of insulin, glucagon and a wide range of gastrointestinal hormones
  • Reference point: the parent molecule for octreotide, lanreotide, pasireotide and the radiolabelled somatostatin-receptor ligands used in neuroendocrine tumour imaging (DOTATATE PET) and therapy
  • Clinical, in some European countries only: the authorised indications are treatment of intestinal and pancreatic fistulae, symptomatic treatment of hypersecretion caused by endocrine tumours of the digestive tract, and treatment of acute oesophageal bleeding where endoscopic sclerotherapy cannot be applied because of the intensity of the bleeding 5
  • Research: infusion is used experimentally to clamp endogenous GH secretion when studying the GH axis

Dosing

Dose
As an intravenous medicine where it is registered: a 250 mcg bolus followed by continuous infusion of approximately 250 mcg per hour (3.5 mcg/kg/h) for gastrointestinal haemorrhage.
Frequency
continuous infusion; there is no intermittent dosing schedule because the half-life is too short
Route
intravenous only
Duration
typically 48-120 hours for acute bleeding, with gradual rather than abrupt withdrawal
  • These figures come from European product information for native somatostatin infusion products 5. There is no subcutaneous, oral or self-administered form of native somatostatin, and there is no legitimate outpatient use — the SmPC states the product is for hospital use, preferably in intensive care 5.
  • In severe renal impairment (creatinine clearance 30 ml/min or below) both the bolus and the infusion rate are halved, to 1.75 mcg/kg and 1.75 mcg/kg/h respectively 5.
  • Abrupt interruption of the infusion can cause a rebound of the treated condition, particularly when treating fistulae; after fistulae have healed the SmPC directs giving only half the dose for a further 48 hours to prevent a possible rebound effect 5.
  • The label advises against giving sugar concurrently where possible and directs regular glucose monitoring: the fall in blood glucose at the start of the infusion may be followed after 2 to 3 hours by a rise, caused by inhibition of insulin secretion. Small doses of insulin may be warranted 5.
  • Because glomerular filtration rate, diuresis and serum sodium can fall during treatment, regular checks of renal function and electrolytes are recommended 5.
  • Anyone looking for a practical somatostatin-pathway therapy is looking for octreotide, lanreotide or pasireotide, not this molecule.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Reconstitution

Vial sizes
0.25 mg, 3 mg, 6 mg (lyophilised powder, hospital infusion products)
Solvent
0.9% sodium chloride for infusion, per the product leaflet
Storage
Powder at 2-8 °C per product leaflet. The reconstituted infusion solution is prepared immediately before use and is not stored.

Worked example

A 3 mg vial reconstituted and diluted into an infusion running at 3.5 mcg/kg/h delivers roughly 12 hours of infusion in a 70 kg adult.

This is a hospital infusion product prepared by pharmacy or nursing staff. Bacteriostatic-water reconstitution schemes written for research peptides do not apply.

This is given as an intravenous infusion, diluted further into a much larger volume. An insulin syringe is not the instrument involved, so no unit conversion is offered here.

Safety

Side effects

  • Nausea, abdominal pain and diarrhoea — spontaneously reported gastrointestinal reactions, which along with flushing occur with rapid injection and can be prevented by injecting slowly 5
  • Hyperglycaemia and hypoglycaemia — both are reported. Somatostatin suppresses insulin as well as glucagon, and the label describes a fall in blood glucose at the start of the infusion that may be followed after 2 to 3 hours by a rise from inhibited insulin secretion 5
  • Hot flushes, hypotension and hypertension — the vascular reactions reported 5
  • Bradycardia and atrioventricular block — the cardiac reactions reported 5
  • Rebound of the treated condition on abrupt interruption of a continuous infusion, particularly when treating fistulae 5
  • A risk of sensitisation if the patient has previously received somatostatin 5
  • Falls in glomerular filtration rate, diuresis and serum sodium during treatment, which is why renal function and electrolytes are monitored 5

Do not use if

  • Hypersensitivity to somatostatin or to any of the excipients — the only formal contraindication in the SmPC 5
  • Pregnancy and breastfeeding — the SmPC states that safe use during pregnancy and breastfeeding has not been established and that somatostatin must therefore not be used in pregnant women, during breastfeeding, or in the pre- or postnatal period 5
  • Caution in patients with diabetes, with regular glucose monitoring during infusion, because the initial fall in blood glucose may be followed by a rise from inhibited insulin secretion 5
  • Severe renal impairment (creatinine clearance 30 ml/min or below) requires halving both bolus and infusion dose 5
  • Arterial bleeding from vessel rupture must be treated surgically, under endoscopic control, rather than with somatostatin 5
  • Not appropriate outside a monitored hospital setting — the SmPC specifies hospital use, preferably in intensive care 5

Interactions

Given the breadth of somatostatin's pharmacodynamic effects on different regulatory systems, many pharmacodynamic interactions are possible. The SmPC identifies potentially clinically important interactions with drugs affecting glucose regulation, plasma renin and arterial blood pressure, noting that somatostatin can modify those drugs' effects on those parameters. Concurrent administration of sugar in any form — glucose or fructose solutions, or total parenteral nutrition — promotes glycaemic disturbance and requires regular glucose monitoring 5. It antagonises growth hormone secretagogues and GHRH analogues directly at the pituitary — this is a pharmacological antagonism at the level of the somatotroph, not a metabolic interaction. It slows gastric emptying and reduces splanchnic blood flow, which can alter the absorption and hepatic first-pass metabolism of oral drugs. Concomitant use with drugs that lower heart rate, such as beta-blockers, may compound bradycardia. Barbiturates given concurrently have been reported to have prolonged effect.

Sources