Somatostatin-25

We have isolated form extracts of ovine hypothalami two molecules characterized as somatostatin-28 and somatostatin-4-28 (referred to as somatostatin-25). They were reproduced by solid hase synthesis. In equimolar ratio and depending upon the experimental conditions, synthetic somatostatin-28 ans somatostatin-25 are 3-14 times more potent than somatostatin-14 to inhibit the basal in vitro secretion of growth hormone or as stimulated by prostaglandin (PGE2). In early studies in vivo, somatostatin-28 and somatostatin-25 are also more potent than somatostatin-14 in inhibiting the secretion of growth hormone acutely stimulated in the rat by injection of morphine; somatostatin-28 is also longer-acting than somatostatin-14. These results suggest that somatostatin-14, as originally isolated, is a biologically active fragment of a larger molecule of greater specific activity; it should be considered as another form of somatostatin with high biological activity present in some tissues and likely secreted y the tissues along with somatostatin-14 and possibly other somatostatin-peptides of diverse sizes.

A specific and sensitive radioimmunoassay (RIA) for the measurement of plasma levels of somatostatin-25 (SS-25) in salmon was developed using antisera raised against coho salmon (Oncorhynchus kisutch) SS-25. Somatostatin-25 was iodinated by the chloramine-T method and repurified on Sephadex G-25. The RIA was performed using a double antibody (goat anti-rabbit gammaglobulin as second antibody) method under disequilibrium conditions. Plasma from several salmonids (coho, chinook, rainbow trout, brook trout, arctic char, lake trout, and whitefish) as well as plasma from some nonsalmonids (sucker, bluegill) cross-reacted with the antisera; serial dilutions of plasma from rainbow trout, brook trout, chinook salmon, and coho salmon were parallel to the SS-25 standard curve. Plasma from catfish showed negligible cross-reactivity. None of the mammalian somatostatins (somatostatin-14, somatostatin-28). U II, or other pancreatic hormones (insulin, glucagon) tested showed significant cross-reactivity with the antibody in the assay system. The lowest detectable level of SS-25 was 5 pg/tube; especially reproducible results were obtained in the range of 0.15-1.20 ng/ml, which appears to be the normal range of SS-25 circulating in the plasma of salmonids. Intra- and interassay coefficients of variation were 5.7 and 12.6%, respectively. Injection of glucose into chinook salmon resulted in an elevation of plasma SS-25 titers within 30 min and was coincident with hyperglycemia.

Previous studies have indicated that teleost fish appear to have two somatostatin genes. In salmonid fish, it is purported that gene I encodes for somatostatin-14 (SS-14), while gene II encodes for somatostatin-25 (sSS-25). In the present study, the physiological effects of SS-14 and sSS-25 on carbohydrate and lipid metabolism in rainbow trout, Oncorhynchus mykiss, were evaluated by in vivo administration of hormone and measuring resulting levels of specific metabolites and hormones present within tissues and plasma. Somatostatin-14 administration caused hyperglycemia without affecting liver glycogen content and increased plasma fatty acid (FA) levels in association with enhanced activity of the lipid mobilizing enzyme, triacylglycerol lipase (TG lipase). Somatostatin-14 injection also resulted in reduced hepatic glucose-6-phosphate dehydrogenase activity, which may indicate a decrease in glucose channeling through the pentose phosphate shunt. In addition, SS-14 reduced plasma glucagon concentration, while having no effect on plasma insulin levels. Salmon SS-25 elevated plasma glucose levels in association with reduced glycogen content and resulted in increased plasma FA levels accompanied by increased hepatic TG lipase activity. Salmon SS-25 injection also resulted in a reduction in plasma glucagon and insulin levels. These results indicate that SS-14 and sSS-25 are important regulators of carbohydrate and lipid metabolism in rainbow trout and that modulation of metabolic activity by these peptides may be accomplished, in part, by alterations in insulin and glucagon levels circulating in the plasma.