Abstract
Somatostatin is a peptide with known antiproliferative effects on the intestine. The aim of the present work was to determine whether somatostatin (SST) antagonism reduces elemental diet-induced intestinal atrophy in the rat. Male Wistar rats were fed a standard diet and treated for seven days with either continuous infusion of saline or low and high doses of a putative somatostatin antagonist; another group was given a SST antagonist in a pulsatile high dose. All these groups received an elemental diet to induce gut mucosa atrophy. Rats were killed and samples were obtained for morphometric and proliferative measurements of the intestine and for SST and insulin-like growth factor-1 (IGF-1) level determination. The elemental diet decreased mucosal length and proliferation. Pulsatile administration of SST antagonist improved or prevented both effects, whereas continuous SST antagonist delivery prevented decreased crypt proliferation induced by the elemental diet. Somatostatin plasma levels were lowest in rats receiving pulsatile administration of SST antagonist. In conclusion, somatostatin antagonism increases proliferation in the intestinal mucosa, improving elemental diet-induced intestinal atrophy; however, morphological growth is not affected.
Similar content being viewed by others
REFERENCES
Dowling RH: Small bowel adaptation and its regulation. Scand J Gastroenterol 17:53–74, 1982
Wood JG, Hoang HD, Bussjaeger LJ, Solomon TE: Neurotensin stimulates growth of small intestine in rats. Am J Physiol 255:G813–G817, 1988
Leblond CP, Carriere R: The effect of growth hormone and thyroxine on the mitotic rate of the intestinal mucosa of the rat. Endocrinology 56:261–266, 1955
Seidel ER, Marcuard S: Stimulation of ileal mucosal growth by insulin-like growth factor I (IGF-1). Digestion 46:288, 1990
Evers BM, Mehrabian H, Townsend CM, Uchida T, Thompson JC: Neurotensin prevents small bowel mucosal atrophy produced by an elemental diet. Surg Forum 40:22–25, 1989
De Miguel E, Gomez de Segura IA, Bonet H, Rodriguez MJ, Mata A: Trophic effects of neurotensin in massive bowel resection in the rat. Dig Dis Sci 39:59–64, 1994
Gomez de Segura IA, Aguilera MJ, Codesal J, Codoceo R, De-Miguel E: Comparative effects of growth hormone in large and small bowel resection in the rat. J Surg Res 62:5–10, 1996
Dunn JCY, Parungo C, Fonkalsrund EW, Mcfadden DW, Ashley SW: Epidermal growth factor selectively enhances functional enterocyte adaptation after massive small bowel resection 1. J Surg Res 67:90–93, 1997
Hart MH, Phares CK, Erdman SH, Grandjean CJ, Park J: Augmentation of postresection mucosal hyperplasia by plerocercoid growth factor (PGF). Analog of human growth hormone. Dig Dis Sci 32:1275–1280, 1987
Byrne TA, Persinger RL, Young LS, Ziegler TR, Wilmore DW: A new treatment for patients with short-bowel syndrome. Growth hormone, glutamine, and a modified diet. Ann Surg 222:243–254, 1995
Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R: Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 179:77–79, 1973
Reichlin S: Somatostatin. N Engl J Med 309:1495–1501, 1983
Reichlin S: Somatostatin (second of two parts). N Engl J Med 309:1556–1563, 1983
Stange EF, Schneider A, Schusdziarra V, Ditschuneit H: Inhibitory effects of somatostatin on growth and differentiation in cultured intestinal mucosa. Horm Metab Res 16:74–78, 1984
Thompson JS, Nguyen BL, Harty RF: Somatostatin analogue inhibits intestinal regeneration. Arch Surg 128:385–389, 1993
Parekh D, Izukura M, Yoshinaga K, Townsend CM, Thompson JC: Endogenous somatostatin is an antitrophic factor for the gut and the pancreas. Digestion 46:125–126, 1990
Bass BL, Fischer BA, Richardson C, Harmon JW: Somatostatin analogue treatment inhibits post-resectional adaptation of the small bowel in rats. Am J Surg 161:107–111, 1991
Engin A, Atlan N, Ercan ZS, Ersoy E, Demirag A: Changes in gastric mucosal histamine and prostaglandin E2-like activities in relation to portal somatostatin following small bowel resection in guinea-pigs. Prostaglandins Leukot Essent Fatty Acids 48:319–321, 1993
Colas B, Bodegas G, Sanz M, Prieto JC, Arilla E: Partial enterectomy decreases somatostatin-binding sites in residual intestine of rabbits. Clin Sci 74:499–505, 1988
Schusdziarra V, Rouiller D, Akimura A, Unger RH: Antisomatostatin serum increases levels of hormones from the pituitary and gut but not from the pancreas. Endocrinology 103:1956–1959, 1978
Fries JL, Murphy WA, Sueiras-Diaz J, Coy DH: Somatostatin antagonist analog increases GH, insulin, and glucagon release in the rat. Peptides 3:811–814, 1982
Bick T, Hochberg Z, Amit T, Isaksson OGP, Jansson JO: Roles of pulsatility and continuity of growth hormone (GH) administration in the regulation of hepatic GH-receptors, and circulating GH-binding protein and insulin-like growth factor-l. Endocrinology 131:423–429, 1992
Hochberg Z, Philip M, Youdim MBH, Amit T: Regulation of the growth hormone (GH) receptor and GH-binding protein by GH pulsatility. Metabolism 42:1617–1623, 1993
Isgaard J, Carlsson L, Isaksson OGP, Jansson JO: Pulsatile intravenous growth hormone (GH) infusion to hypophysectomized rats increases insulin-like growth factor l messenger ribonucleic acid in skeletal tissues more effectively than continuous GH infusion. Endocrinology 123:2605–26010, 1988
Tannembaum GS, Rorstad O, Brazeau P: Effects of prolonged food deprivation on the ultradian growth hormone rhythm and immunoreactive somatostatin tissue levels in the rat. Endocrinology 104:1733–1738, 1979
Tannenbaum GS, Ling N: The interrelationship of growth hormone (GH)-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion. Endocrinology 115:1952–1957, 1984
Turner JP, Tannenbaum GS: In vivo evidence of a positive role for somatostatin to optimize pulsatile growth hormone secretion. Am J Physiol 269:E683–E690, 1995
Rebuffat P, Belloni AS, Musajo FG, Rocco S, Markowska A, Mazzochi G, Nussdorfer GG: Evidence that endogenous somatostatin (SRIF) exerts an inhibitory control on the function and growth of rat adrenal zona glomerulosa. The possible involvement of zona medullaris as a source of endogenous SRIF. J Steroid Biochem Mol Biol 48:353–360, 1994
Rosekrans PC, Meijer CJ, Comelisse CJ, van der Wal AM, Lindeman J: Use of morphometry and immunohistochemistry of small intestinal biopsy specimens in the diagnosis of food allergy. J Clin Pathol 33:125–130, 1980
Lehy T, Dubrasquet M, Bonfils S: Effect of somatostatin on normal and gastrin stimulated cell proliferation in the gastric and intestinal mucosa of the rat. Digestion 19:99–109, 1979
Conteas CN, Majumdar APN: The effects of gastrin, epidermal growth factor and somatostatin on DNA synthesis in a small intestinal crypt cell line (IEC-6). Proc Soc Exp Biol Med 184:307–311, 1987
Sgambati SA, Zarif A, Basson MD: Octreotide differentially modulates human Caco-2 intestinal epithelial cell proliferation and differentiation by decreasing intracellular camp. Regul Pept 61:219–227, 1996
Kirkegaard P, Olsen PS, Nexo E, Hoist JJ, Poulsen SS: Effect of vasoactive intestinal polypeptide and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner' glands. Gut 25:1225–1229, 1984
Thompson JC: Humoral control of gut function. Am J Surg 161:6–18, 1991
Luo Q, Peyman GA, Conway MD, Woltering EA: Effect of a somatostatin analog (octreotide acetate) on the growth of retinal pigment epithelial cells in culture. Curr Eye Res 15:909–913, 1996
Lauder H, Sellers LA, Fan TP, Feniuk W, Humphrey PP: Somatostatin sst5 inhibition of receptor mediated regeneration of rat aortic vascular smooth muscle cells. Br J Pharmacol 122:663–670, 1997
Schedl HP, Wilson HD, Solomon TE: Gastrin, somatostatin, and alimentary tract growth responses to small intestinal resection in the rat. Digestion 41:237–244, 1988
Konturek SJ, Brzozowski T, Dembinski A, Warzecha Z, Konturek PK, Yanaihara N: Interaction of growth hormonereleasing factor and somatostatin on ulcer healing an mucosal growth in rats: role of gastrin and epidermal growth factor. Digestion 41:121–128, 1988
Vanderhoof JA, Kollman KA: Lack of inhibitory effect of octreotide on intestinal adaptation in short bowel syndrome in the rat. J Pediatr Gastroenterol Nutr 26:241–244, 1998
Gomez de Segura IA, Prieto I, Grande AG, Garcia P, Guerra A, Mendez J, De-Miguel E: Growth hormone reduces mortality and bacterial translocation in irradiated rats. Acta Oncol 37:179–185, 1998
Gomez de Segura IA, Marijuan, Trillo P, Picornell M, Codoceo R, Diaz J, De Miguel E: Evolucion de los niveles plasmaticos de peptidos reguladores intestinales tras reseccion de colon en la rata. Rev Esp Enterm Dig 87:20–24, 1995
Wiren M, Skullman S, Wang F, Permert J, Larsson J: Intraluminal glutamine refeeding supports mucosal growth in rat jejunum. Transplant Proc 26:1460–1463, 1994
Arimura A, Smith WD, Schally AV: Blockade of the stressinduced decrease in blood GH and antisomatostatin serum in rats. Endocrinology 98:540–543, 1976
Ulshen MH, Dowling RH, Fuller CR, Zimmermann EM, Lund PK: Enhanced growth of small bowel in transgenic mice overexpressing bovine growth hormone [see comments]. Gastroenterology 104:973–980, 1993
Dahistrom KA, Durant M, Chan E, Rosenfeld R, Castillo R: Abnormal intestinal adaptation to small bowel resection in growth hormone (GH) deficient rats. Nutr Hosp 9:225, 1994
Lobie PE, Breipohl W, Waters MJ: Growth hormone receptor expression in the rat gastrointestinal tract. Endocrinology 126:299–306, 1990
Dahlstrom KA, Durant M, Chan E, Rosenfeld R, Castillo R: Abnormal intestinal adaptation to small bowel resection in growth hormone (GH) deficient rats. Nutr Hosp 9:225, 1994
Shulman DI, Hu CS, Duckett G, Lavallee-Grey M: Effects of short-term growth hormone therapy in rats undergoing 75% small intestinal resection. JPEN 14:3–11, 1992
Benhamou PH, Canarelli JP, Leroy C, De Boissieu D, Dupont C: Stimulation by recombinant human growth hormone of growth and development of remaining bowel after subtotal ileojejunectomy in rats. JPEN 18:446–452, 1994
Ohneda K, Ulshen MH, Fuller CR, D'Ercole AJ, Lund PK: Enhanced growth of small bowel in transgenic mice expressing human insulin-like growth factor I. Gastroenterology 112: 444–454, 1997
Maton PN: The use of the long-acting somatostatin analogue octreotide acetate, in patients with islet cell tumors. Gastroenterol Clin North Am 18:827–922, 1989
Krempels K, Hunyady B, OqCarroll AM, Mezey E: Distribution of somatostatin receptor messenger RNAs in the rat gastrointestinal tract. Gastroenterology 112:1948–1960, 1997
Coy DH, Murphy WA, Raynor K, Reisine T: The new pharmacology of somatostatin and its multiple receptors. J Pediatr Endocrinol 6:205–209, 1993
Warhurst G, Higgs NB, Fakhoury H, Warhurst AC, Garde J, Coy DH: Somatostatin receptor subtype 2 mediates somatostatin inhibition of ion secretion in rat distal colon. Gastroenterology 111:325–333, 1996
Buscail L, Saint-Laurent N, Chastre E, Vaillant JC, Gespach C, Capella G, Kalthoff H, Lluis F, Vaysse N, Susini C: Loss of sst2 somatostatin receptor gene expression in human pancreatic and colorectal cancer. Cancer Res 56:1823–1827, 1996
Cordelier P, Esteve JP, Bousquet C, Delesque N, OqCarroll AM, Schally AV, Vaysse N, Susini C, Buscail L: Characterization of the antiproliferative signal mediated by the somatostatin receptor subtype sst5. Proc Natl Acad Sci USA 94: 9343–9348, 1997
Laws SA, Gough AC, Evans AA, Bains MA, Primrose JN: Somatostatin receptor subtype mRNA expression in human colorectal cancer and normal colonic mucosae. Br J Cancer 75:360–366, 1997
Gyr KE, Meier R: Pharmacodybamic effects of sandostatin in the gastrointestinal tract. Digestion 54(suppl):1–19, 1993
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gómez de Segura, I., Castell, T., Vázquez, I. et al. Somatostatin Antagonism Prevents Elemental Diet-Induced Intestinal Atrophy in the Rat. Dig Dis Sci 46, 1985–1992 (2001). https://doi.org/10.1023/A:1010655703003
Issue Date:
DOI: https://doi.org/10.1023/A:1010655703003