Somatostatin Receptors

The five somatostatin receptors (SSTR1 through SSTR5) belonging to the family of neuroendocrine receptors are widely expressed in pituitary gland, spleen, and the gastrointestinal tract.27 Somatostatin exists as two biologically active forms (SS-14 and SS-28) and inhibits secretion of growth hormone (GH) from the pituitary gland. The pituitary gland is crucial for the maintenance of several homeostatic functions including growth, metabolism, and reproduction. Since pituitary tumors are associated with unrestrained secretion and action of trophic hormones, treatment is aimed at the suppression of hormone hypersecretion, inhibition, and prevention of pituitary tumor growth.16,28 Pituitary tumors account for 15% of intracranial tumors and are usually benign and nonmetastatic.

The high expression levels of SSTR2 and SSTR5 in pituitary adenomas29 make them attractive targets for drug development. Octreotide and lanreotide, synthetic somatostatin analogs targeting these receptors, have longer half-lives than native somatostatin and are used currently in the treatment of pituitary tumors. Novel somatostatin analogs with affinity for SSTR1 and SSTR3 are also under consideration; SSTR1 has been linked to inhibition of cell cycle progression and SSTR3 signaling can induce apoptosis.30 Cytotoxic analogs of somatostatin, consisting of radicals conjugated to peptide carriers, can also be used to target these receptors in tumors.31 However, somatostatin and receptor subtypes are expressed in various normal and neoplastic tissues32 and require selective targeting.

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