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Structure, Synthesis, and Secretion of Somatostatin
Somatostatin (SS) initially was isolated from the hypothalamus as a peptide that inhibits the secretion of growth hormone. It has since been isolated and identified in the GI tract and in the endocrine pancreas. Regardless of its source, its synthesis and structure appears to be identical. SS is synthesized as a 116 amino acid preprohormone that is subsequently cleaved to a 14- or 28-amino acid compound. SS-14 predominates in the hypothalamus and endocrine pancreas, but SS-28 is most abundant in the GI tract. Unlike most prohormones, SS-28 is more biologically active in the endocrine pancreas than SS-14. In the islets, D cells secreting SS are in close proximity to A and B cells. It is thought that SS acts as a parahormone to inhibit insulin or glucagon, depending on the physiologic situation. These cells are connected to one another by gap junctions, and it has been shown that SS is released at the junctions where it elicits its action. In the GI tract SS secretion is paracrine or endocrine. Some SS may be secreted into the capillaries and then act like a conventional hormone. At the hypothalamus, SS is secreted into the median eminence and into the portal system to inhibit GH release; in this case it acts like a neurohormone. Immunohistochemistry studies indicate that SS is found in vesicles of neurons in the CNS and peripheral nervous system suggesting that SS also functions as a neurotransmitter and/or neuromodulator. Regardless of its source, its action is always inhibitory.
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