Somatostatin (SST) is a small cyclic peptide that was first identified as a powerful inhibitor of the secretion of various hormones including growth hormone (GH), thyroid-stimulating hormone (TSH) and prolactin from the pituitary, as well as almost every major hormone from the intestinal tract. SST consists of two major bioactive forms, SST-14 and the N-terminus extended peptide SST-28 that can be produced by a wide variety of neuroendocrine, inflammatory and immune cells. In target cells, SST induces a variety of physiological functions that include neuromodulation, cell secretion, cell proliferation and smooth muscle contractility.

SST acts on its multiple cell targets via a family of six receptors that originate from five genes: SSTR1, SSTR2a, SSTR2b, SSTRR3, SSTR4, SSTR5. The SSTRs are members of the G-protein coupled receptor superfamily and they modulate cell responses via multiple second messenger systems such as inhibition of adenylate cyclase, modulation of conductance of ion channels and protein dephosphorylation.

SSTRs are expressed widely in both the brain and peripheral tissues but with receptor subtype variations between the different cell types. SSTR4 is the SSTR subtype least expressed in the brain but is most strongly expressed in the lung, heart and placenta.

Strong SSTR expression has been detected in a variety of human tumors including pancreatic, breast, lung and prostate cancers. In fact, SST has been shown to inhibit the growth of various normal and tumor cells. On this basis, several long lasting SST analogs have been developed and are being tested for use in several pathologies such as various cancers, acromegaly, immunoproliferative disorders, diabetic retinopathy, epilepsy and pain.