Somatostatin and somatostatin receptor physiology.

Since the discovery of somatostatin (SST) over three decades ago, its ubiquitous distribution and manifold functions are still being documented. SST is synthesized in the hypothalamus and transported to the anterior pituitary gland where it tonicaly inhibits GH and TSH secretion as well as being responsible for GH pulsatile release. Several internal feedback loops, sleep, exercise, and chemical agents control and influence SST release. SST also impacts the function of a wide variety of cells and organ systems throughout the body. Knowledge of the structures of the SSTs has resulted in recognition of the essential four core conserved residues responsible for their actions. The SSTs act through six separate SST cell surface receptors (SSTRs), members of the family of G protein-coupled receptors. Receptor ligand binding (SST/SSTR) results in cellular activities specific for each receptor, or receptor combinations, and their tissue/cell localization. Understanding the structure/function relationship of the SSTs and their receptors, including the internalization of SST/SSTR complexes, has facilitated the development of a variety of novel pharmacologic agents for the diagnosis and treatment of neuroendocrine tumors and unfolding new applications.