5 - The structure and regulation of the somatostatin gene

Summary

Introduction

Somatostatin is a tetradecapeptide that regulates the release of pituitary, pancreatic, and gastrointestinal hormones (Reichlin, 1983, 1987). Initially identified in the hypothalamus as an inhibitor of growth hormone secretion (Brazeau et al., 1973), somatostatin has subsequently been found in the extrahypothalamic brain, spinal cord, retina, gastrointestinal tract, pancreatic islets, and thyroid (Patel & Reichlin, 1978; Arimura et al, 1975; Rorstad et al, 1979; Hökfelt et al, 1975). In addition to inhibiting the secretion of a number of pep tide hormones, somatostatin has been proposed to act as a neurotransmitter and to modulate gastrointestinal motility (Barker, 1976; Gerich & Patton, 1978).

The diverse functions and the widespread distribution of the tetradecapeptide somatostatin (somatostatin-14) have focused attention on the biosynthesis of the hormone. Several studies have shown that somatostatin- 14 is synthesized as part of a larger precursor. A 28-amino acid form of the hormone (somatostatin-28) has been identified in extracts of porcine hypothalamus (Schally et al, 1980), gastrointestinal tract (Pradayrol et al., 1980) and bovine hypothalamus (Esch et al., 1980). The biological actions of somatostatin-28 are similar to those of somatostatin- 14 but in addition the larger peptide may have functions distinct from those of the tetradecapeptide (Meyers et al., 1980; Mandarino et al., 1981; Browne et al., 1981).

The amino acid sequence of somatostatin-14 has been conserved remarkably well throughout evolution; the sequences of the fish and mammalian (human and rat) peptides are identical (Fig. 5.1). The variety of somatostatin-related peptides present in the animal kingdom, however, is quite diverse.