ABSTRACT
In 1977, Guillemin and Schally were awarded a portion of the Nobel Prize in Medicine and Physiology for the identification of somatostatin and other hypothalamic regulatory peptides. Somatostatin is a 14-amino-acid peptide (with 12 of the amino acids arranged in a ring structure) that inhibits the secretion of growth hormone (or somatotropin; hence, somato statin) by the anterior pituitary. Somatostatin was also observed to have an effect on a number of processes throughout the body, including inhibition of smooth muscle contraction and hormonal secretion. These peripheral effects correlated with the expression of specific somatostatin receptors on tissues and cells throughout the body. In humans, five different subtypes of somatostatin receptors have been identified and cloned. Tumors that arose from neuroendocrine tissue had an increased expression of somatostatin receptors, most commonly
receptor subtypes 2 and 5 (SSTR2; SSTR5). In order to evaluate the therapeutic potential of this inhibitory peptide, a variety of analogs that had high binding affinity to somatostatin receptors but a longer biologic effect were synthesized as they had greater resistance to the peptidases responsible for somatostatin’s short biologic half-life.
