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Gene Review

SST  -  somatostatin

Ovis aries

Synonyms: PPS, SOM14, SRIF
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Disease relevance of SRIF

  • The SRIF analogue had no effect on plasma ACTH in the same animals in control experiments with no hemorrhage [1].
  • This study reports semiquantitative estimates of the noradrenergic input to neuroendocrine GHRH and SRIF neurones in the sheep of different body weights [2].
  • Pretreatment of the cells with pertussis toxin (100 nmol/L) overnight abolished the Ca2+ current response to SRIF [3].
  • Measurement of growth hormone-releasing hormone and somatostatin in hypothalamic-portal plasma of unanesthetized sheep. Spontaneous secretion and response to insulin-induced hypoglycemia [4].
  • An additional infusion of somatostatin into hyperglycemic fetuses blocked fetal hyperinsulinemia and completely prevented these increases, specifying insulin as the causative factor [5].

High impact information on SRIF


Chemical compound and disease context of SRIF

  • Omeprazole (a proton pump inhibitor) increased gastric pH to a similar extent in both the control and immunized groups but resulted in a smaller increase in plasma gastrin in the immunized sheep, thus calling into question the assumption that hypergastrinemia associated with hypochlorhydria is the result of somatostatin withdrawal [9].

Biological context of SRIF

  • GH secretion is also affected by alteration in adiposity, which could be via modulation of GHRH and SRIF cells [10].
  • In fetuses of 115-122 days gestation, SRIF had no detectable effect on the oGH response to GRF [peak incremental oGH response (mean +/- SEM), 527 +/- 124 vs. 562 +/- 103 ng/ml in controls] [11].
  • The lack of sex differences in circulating patterns of SRIF in portal plasma implies that there may be a difference in GRF secretion which may produce sexually dimorphic patterns of GH secretion in lamb [12].
  • Net total splanchnic alpha-amino N release and oxygen consumption were decreased (P < .10) with exogenous SRIF, but CSH increased (P < .05) insulin release and oxygen consumption [13].
  • The lambs that received immunization alone produced significant antibody titers against SRIF, whereas 9 of the 10 clenbuterol-treated lambs produced no significant, specific antibody response [14].

Anatomical context of SRIF

  • SRIF secretion is increased by gastric acidity and also directly by regulators of gastric acid secretion such as gastrin [15].
  • Restricted feeding had no affect on GRF secretion, but because of the reduced exposure of the pituitary gland to SRIF, it is possible that responsiveness to GRF is enhanced [16].
  • To ascertain the extent to which leptin may act on these neurons, we have used immunohistochemistry to examine co-localization of long-form of the leptin receptor (OB-Rb) and SRIF in the sheep hypothalamus [17].
  • Pancreatic somatostatin at 100 ng/ml produced a 50-60% inhibition of insulin and glucagon secretion from perfused rat pancreas, while SRIF produced comparable inhibition at 10 ng/ml [18].
  • Inhibition of 125I-labelled tyr1-SRIF binding to bovine pituitary plasma membranes by catfish pancreatic somatostatin was approximately 33% that of SRIF [18].

Associations of SRIF with chemical compounds

  • These results indicate that in the fetus, gastrin receptors, but not histamine receptors, are functionally involved in the stimulation of SRIF secretion [15].
  • The SRIF stimulatory effect of pentagastrin in 28-day-old lambs was abolished by ranitidine, which also reduced this effect in the adult sheep [15].
  • However, after discontinuing SRIF, late increases in TSH, T4 and T3 were observed [19].
  • The results indicate that the hyperiodothyroninemia characteristic of the newborn period does not block the response to exogenous TRH, whereas the inhibitory effect of exogenous SRIF is observed in the newborn as in the adult [19].
  • Injection of SRIF antiserum (oA-SRIF) increases serum GH and TSH levels in urethane-anesthetized rats [20].

Regulatory relationships of SRIF


Other interactions of SRIF

  • Pulses of SRIF were not significantly associated with changes in GH or GRF concentrations [16].
  • The percentage of SRIF cells receiving GHRH, neuropeptide Y, GAL, and orexin afferents was higher in lean animals [10].
  • Propionate (0.5 mmole per kilogram) and arginine (10 gm.) induced a rise in plasma insulin and GH, and glucagon was effectively blocked by cyclic somatostatin (0.5 mg.). Similarly, somatostatin inhibited glucose, and glucagon provoked GH and insulin secretory responses without affecting glucose or FFA levels [8].
  • Using immunocytochemical approaches, the present study revealed that although somatostatin neurons were located in several hypothalamic sites, only those in the arcuate nucleus (13% +/- 2%) and ventromedial nucleus (VMN; 29% +/- 1%) expressed ERalpha [23].
  • Forskolin, an activator of adenylate cyclase, has been used to investigate the effects of raising pituitary cell cyclic AMP concentrations on prolactin and growth hormone secretion and to examine the role of cyclic AMP in the inhibitory actions of dopamine and somatostatin [22].

Analytical, diagnostic and therapeutic context of SRIF

  • Passive immunization with a specific antiserum to SRIF in males resulted in significant elevation of GH nadir levels but had no effect on GH peak amplitude [24].
  • Gel chromatography of pooled -7 d abomasal tissue extracts showed five peaks of SRIF immunoreactivity; the predominate peak eluted in the same position as synthetic SRIF-14 [25].
  • Although two analogues were shown to be significantly more potent than SRIF (p less than 0.01), in this sheep bioassay the duration of action did not appear to be longer than that of the native hormone for any of the three analogues [26].
  • These peptides have reduced immunoreactivity in a radioimmunoassay for synthetic somatostatin, but full biological activity was measured as inhibition of growth hormone released from isolated rat anterior pituitary cells [7].
  • Using in situ hybridization, we showed that this short estradiol treatment increased the somatostatin mRNA amount by about 50% in the VMN and 42% in the IN [27].


  1. Intracerebroventricular infusion of a cyclic hexapeptide analogue of somatostatin inhibits hemorrhage-induced ACTH release. Wang, X.M., Tresham, J.J., Coghlan, J.P., Scoggins, B.A. Neuroendocrinology (1987) [Pubmed]
  2. Noradrenergic regulation of hypothalamic cells that produce growth hormone-releasing hormone and somatostatin and the effect of altered adiposity in sheep. Iqbal, J., Manley, T.R., Yue, Q., Namavar, M.R., Clarke, I.J. J. Neuroendocrinol. (2005) [Pubmed]
  3. G(o)2 and Gi3 proteins mediate the action of somatostatin on membrane Ca2+ and K+ currents in ovine pituitary somatotrophs. Chen, C. Clin. Exp. Pharmacol. Physiol. (1997) [Pubmed]
  4. Measurement of growth hormone-releasing hormone and somatostatin in hypothalamic-portal plasma of unanesthetized sheep. Spontaneous secretion and response to insulin-induced hypoglycemia. Frohman, L.A., Downs, T.R., Clarke, I.J., Thomas, G.B. J. Clin. Invest. (1990) [Pubmed]
  5. Fetal hyperinsulinemia increases farnesylation of p21 Ras in fetal tissues. Stephens, E., Thureen, P.J., Goalstone, M.L., Anderson, M.S., Leitner, J.W., Hay, W.W., Draznin, B. Am. J. Physiol. Endocrinol. Metab. (2001) [Pubmed]
  6. Depolarization- and ionophore-induced release of octacosa somatostatin from stalk median eminence synaptosomes. Kewley, C.F., Millar, R.P., Berman, M.C., Schally, A.V. Science (1981) [Pubmed]
  7. Amino acid sequence of catfish pancreatic somatostatin I. Oyama, H., Bradshaw, R.A., Bates, O.J., Permutt, A. J. Biol. Chem. (1980) [Pubmed]
  8. Studies on growth hormone secretion. VII. Effects of somatostatin on plasma GH, insulin, and glucagon in sheep. Bryce, D., Yeh, M., Funderburk, C., Todd, H., Hertelendy, F. Diabetes (1975) [Pubmed]
  9. Active immunization against somatostatin alters regulation of gastrin in response to gastric acid secretagogues. Westbrook, S.L., McDowell, G.H., Hardy, K.J., Shulkes, A. Am. J. Physiol. (1998) [Pubmed]
  10. Reduction in adiposity affects the extent of afferent projections to growth hormone-releasing hormone and somatostatin neurons and the degree of colocalization of neuropeptides in growth hormone-releasing hormone and somatostatin cells of the ovine hypothalamus. Iqbal, J., Manley, T.R., Ciofi, P., Clarke, I.J. Endocrinology (2005) [Pubmed]
  11. Hormone ontogeny in the ovine fetus and neonate. XXII. The effect of somatostatin on the growth hormone (GH) response to GH-releasing factor. de Zegher, F., Daaboul, J., Grumbach, M.M., Kaplan, S.L. Endocrinology (1989) [Pubmed]
  12. GH, GH-releasing factor and somatostatin in the growing lamb: sex differences and mechanisms for sex differences. Gatford, K.L., Fletcher, T.P., Rao, A., Egan, A.R., Hosking, B.J., Clarke, I.J. J. Endocrinol. (1997) [Pubmed]
  13. Effects of exogenous somatostatin and cysteamine on net nutrient flux across the portal-drained viscera and liver of sheep during intraduodenal infusion of starch hydrolysate and casein. McLeod, K.R., Bauer, M.L., Harmon, D.L., Reynolds, C.K., Mitchell, G.E. J. Anim. Sci. (1997) [Pubmed]
  14. Suppression of immune response in lambs during treatment with the beta-adrenergic agonist clenbuterol. Spencer, G.S., Oliver, M.H. J. Anim. Sci. (1996) [Pubmed]
  15. Developmental regulation of gastric somatostatin secretion in the sheep. Grabau, B.J., Zavros, Y., Hardy, K.J., Shulkes, A. Endocrinology (1999) [Pubmed]
  16. Effect of restricted feeding on the relationship between hypophysial portal concentrations of growth hormone (GH)-releasing factor and somatostatin, and jugular concentrations of GH in ovariectomized ewes. Thomas, G.B., Cummins, J.T., Francis, H., Sudbury, A.W., McCloud, P.I., Clarke, I.J. Endocrinology (1991) [Pubmed]
  17. Localization of long-form leptin receptor in the somatostatin-containing neurons in the sheep hypothalamus. Iqbal, J., Pompolo, S., Murakami, T., Clarke, I.J. Brain Res. (2000) [Pubmed]
  18. The biological activity of catfish pancreatic somatostatin. Oyama, H., Martin, J., Sussman, K., Weir, G.C., Permutt, A. Regul. Pept. (1981) [Pubmed]
  19. The response of newborn sheep to TRH with and without somatostatin. Sack, J., Fisher, D.A., Grajwer, L.A., Lam, R.W., Wang, C.C. Endocrinology (1977) [Pubmed]
  20. Antiserum to rat growth hormone (GH)-releasing factor suppresses but does not abolish antisomatostatin-induced GH release in the rat. Thomas, C.R., Groot, K., Arimura, A. Endocrinology (1985) [Pubmed]
  21. Effects of hypothalamic hormones (GRF, TRH, somatostatin) and insulin-like growth factor I on growth hormone secretion from prepubertal male lamb pituitary cultures. Blanchard, M.M., Goodyer, C.G., Charrier, J., Dulor, J.P., Barenton, B. Reproduction, nutrition, development. (1987) [Pubmed]
  22. Dopamine and somatostatin inhibit forskolin-stimulated prolactin and growth hormone secretion but not stimulated cyclic AMP levels in sheep anterior pituitary cell cultures. Ray, K.P., Gomm, J.J., Law, G.J., Sigournay, C., Wallis, M. Mol. Cell. Endocrinol. (1986) [Pubmed]
  23. Somatostatin-14 neurons in the ovine hypothalamus: colocalization with estrogen receptor alpha and somatostatin-28(1-12) immunoreactivity, and activation in response to estradiol. Scanlan, N., Dufourny, L., Skinner, D.C. Biol. Reprod. (2003) [Pubmed]
  24. Sexual dimorphism of somatostatin and growth hormone-releasing factor signaling in the control of pulsatile growth hormone secretion in the rat. Painson, J.C., Tannenbaum, G.S. Endocrinology (1991) [Pubmed]
  25. Cysteamine-induced depletion of somatostatin in sheep: time course of depletion and changes in plasma metabolites, insulin, and growth hormone. McLeod, K.R., Harmon, D.L., Schillo, K.K., Mitchell, G.E. J. Anim. Sci. (1995) [Pubmed]
  26. Suppression and stimulation of growth hormone release in sheep by somatostatin analogs. Redekopp, C., Livesey, J., Donald, R.A. J. Endocrinol. Invest. (1984) [Pubmed]
  27. Regulation by estradiol of hypothalamic somatostatin gene expression: possible involvement of somatostatin in the control of luteinizing hormone secretion in the ewe. Pillon, D., Caraty, A., Fabre-Nys, C., Lomet, D., Cateau, M., Bruneau, G. Biol. Reprod. (2004) [Pubmed]
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