Somatostatin biosynthesis and release in the hypothalamus and pancreas of the rat

Somatostatin has been localized in several cells of neuroectodermal origin by immunocytochemistry and radioimmunoassay and is presumably synthesized and secreted locally, thereby fulfilling some of the characteristics of a neurotransmitter or neuromodulator. 1,2 Recent studies in perfused dog pancreas and isolated rat islets indicate that somatostatinlike immunoreactivity (SLI) is secreted from D cells and its presence in the human cerebral spinal fluid implies release from peptidergic neurons. 3–6 That peptide biosynthesis occurs by ribosomal mechanisms followed by posttranslational enzyme-mediated cleavage eventuating in peptides destined for secretion has been well established. 7 Although nonribosomal synthesis of conventional neurotransmitters occurs and has been implicated in the synthesis of thyrotropin-releasing hormone and luteinizing hormone-releasing hormone, 8 most evidence favors their biosynthesis through cleavage of large molecular weight precursors. 9,10 The mechanisms of biosynthesis and release of somatostatin have not been elucidated. We present preliminary data in the rat consistent with the notion that hypothalamic neurons and the pancreatic D cell synthesize and release somatostatin through posttranslational scission of precursor polypeptides.