Chemical Identity

Somatostatin-14 (SST-14)

Property	Value
Name	Somatostatin-14
Gene	SST (chromosome 3q27.3)
Sequence	Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys
Length	14 amino acids
Disulfide Bond	Cys3-Cys14 (cyclic)
MW	1637.9 Da
PDB Structures	1SOI (NMR)

Somatostatin-28 (SST-28)

Property	Value
Name	Somatostatin-28
Length	28 amino acids
Sequence	Ser-Ala-Asn-Ser-Asn-Pro-Ala-Met-Ala-Pro-Arg-Ser-Arg-Lys-Ala-Met-Gly-Lys-Lys-Ser-Ala-Gly-Gln-Lys-Arg
MW	3149.7 Da

Receptors

Receptor	Gene	Distribution	Effects
SSTR1	SST1R	Brain, GI tract	↓ GH, antiproliferative
SSTR2	SST2R	Anterior pituitary, GI tract	↓ GH, ↓ gastrin
SSTR3	SST3R	Brain, GI tract	↓ GH, pro-apoptotic
SSTR4	SST4R	Brain, CNS	Neuroprotective
SSTR5	SST5R	Anterior pituitary	↓ GH, ↓ TSH

Physiological Functions

Growth Hormone Regulation

• Primary role: Inhibits GH release from anterior pituitary
• Mechanism: Activates SSTR2/SSTR5 → ↓ cAMP → ↓ GH secretion
• Negative feedback: GH → IGF-1 → somatostatin release

GI Function

• Inhibits: Gastric acid, pepsin, secretin, CCK, VIP, motilin
• Stimulates: Absorption of water and electrolytes
• Modulates: GI motility, pancreatic secretion

Other Functions

• Thyroid: Inhibits TSH release
• Pancreas: Inhibits insulin and glucagon
• CNS: Neurotransmitter, modulates neuronal activity

Clinical Applications

Somatostatin Analogs

Drug	Receptor Profile	Indication
Octreotide (Sandostatin)	SSTR2 > SSTR5	Acromegaly, carcinoid
Octreotide LAR	SSTR2 > SSTR5	Long-acting (monthly)
Lanreotide (Somatuline)	SSTR2 > SSTR5	Acromegaly, NET
Pasireotide (Signifor)	SSTR1/2/3/5	Cushing’s disease
Vapreotide	SSTR2 > SSTR5	Variceal bleeding

Indications

• Acromegaly: Suppresses GH hypersecretion
• Neuroendocrine tumors (NETs): Antiproliferative effects
• Variceal bleeding: Reduces splanchnic blood flow
• Cushing’s disease: Pasireotide (SSTR5-selective)

Manufacturing

• SPPS (Fmoc): Standard solid-phase synthesis
• Disulfide formation: Air oxidation or glutathione buffer
• Purification: RP-HPLC
• Octreotide: D-Trp replacing Trp at position 8, TFA replacing Thr at C-terminus

References

1. Brazeau P, et al. “Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone.” Science 182:1265-1267, 1973. doi:10.1126/science.182.4117.1265
2. Schonbrunn A, Tashjian AH. “Characterization of functional somatostatin receptors.” Journal of Biological Chemistry 253:6471-6478, 1978.
3. Lamberts SWJ, et al. “Octreotide.” New England Journal of Medicine 334:246-254, 1996.
4. Weckbecker G, et al. “Somatostatin analogs for tumor diagnosis and treatment.” Trends in Pharmacological Sciences 24:428-435, 2003.
5. Patel YC. “Somatostatin and its receptor family.” Frontiers in Neuroendocrinology 20:1-43, 1999.