Journal of Comparative Physiology B

, Volume 162, Issue 7, pp 575–580 | Cite as

Inhibition of growth hormone synthesis by somatostatin in cultured pituitary of rainbow trout

  • Takashi Yada
  • Tetsuya Hirano


When the pituitary of rainbow trout (Oncorhynchus mykiss) was incubated in a serum-free medium, a high level of growth hormone release as well as an activation of growth hormone synthesis were observed, suggesting the existence of hypothalamic inhibitory factor(s) on growth hormone synthesis. Although an inhibitory effect of somatostatin on growth hormone release is well established in both mammals and teleosts, an effect on growth hormone synthesis has not been demonstrated. In this study, we examined the effect of somatostatin on growth hormone synthesis in organ-cultured trout pituitary using immunoprecipitation and Northern blot analysis. Somatostatin inhibited growth hormone release from the cultured pituitary within 10 min after addition without affecting prolactin release. Incubation of the pituitary with somatostatin also caused a significant reduction in newly-synthesized growth hormone in a dose-related manner, as assessed by incorporation of [3H]leucine into immunoprecipitable growth hormone. There were no changes in the level or molecular length of growth hormone mRNA after somatostatin treatment, as assessed by Northern slot blot and Northern gel blot analyses. Human growth hormone-releasing factor stimulated growth hormone release, although the spontaneous synthesis of growth hormone was not augmented. However, somatostatin-inhibited growth hormone synthesis was restored by growth hormone-releasing factor to the control level. The spontaneous increase in growth hormone synthesis observed in the organ-cultured trout pituitary may be caused, at least in part, by the removal of the inhibitory effect of hypothalamic somatostatin.

Key words

Growth hormone Somatostatin Pituitary Synthesis Rainbow trout, Oncorhynchus mykiss 



growth hormone


GH-releasing factor




sodium dodecyl sulphate


somatostatin (somatropin release-inhibiting factor)


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Andrews PC, Dixon JE (1981) Isolation and structure of a peptide hormone predicted from a mRNA sequence. J Biol Chem 256:8267–8270Google Scholar
  2. Barinaga M, Yamanoto G, Rivier C, Vale W, Evans R, Rosenfeld MG (1983) Transcriptional regulation of growth hormone gene expression by growth hormone-releasing factor. Nature 306:84–85Google Scholar
  3. Barinaga M, Bilezikijian LM, Vale WW, Rosenfeld MG, Evans RM (1985) Independent effects of growth hormone releasing factor on growth hormone release and gene transcription. Nature 314:279–281Google Scholar
  4. Batten TFC, Young G, Ball JN (1983) Secretory activity of Poecilia latipinna (Teleostei) pituitary in vitroL rostral pars distalis and proximal pars distalis. Gen Comp Endocrinol 51:113–130Google Scholar
  5. Berelowitz M, Szabo M, Frohman LA, Firestone S, Chu L (1981) Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary. Science 212:1279–1281Google Scholar
  6. Bolton JP, Takahashi A, Kawauchi H, Kubota J, Hirano T (1986) Development and validation of a salmon growth hormone radioimmunoassay. Gen Comp Endocrinol 62:230–238Google Scholar
  7. Cao O-P, Duguay SJ, Plisetskaya E, Steiner DF, Chan SJ (1989) Nucleotide sequence and growth hormone-regulated expression of salmon insulin-like growth factor I mRNA. Mol Endocrinol 3:2005–2010Google Scholar
  8. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159Google Scholar
  9. Cook AF, Peter RE (1984) The effects of somatostatin on serum growth hormone levels in the goldfish, Carassius auratus. Gen Comp Endocrinol 54:109–113Google Scholar
  10. Dubois MP, Billard R, Breton B, Peter RE (1979) Comparative distribution of somatostatin, LH-RH, neurophysin, and α-endorphin in the rainbow trout: an immunocytological study. Gen Comp Endocrinol 37:220–232Google Scholar
  11. Fryer JN, Nishioka RS, Bern HA (1979) Somatostatin inhibition of teleost growth hormone secretion. Gen Comp Endocrinol 39:244–246Google Scholar
  12. Fukata J, Diamond DJ, Martin JB (1985) Effects of rat growth hormone (rGH)-releasing factor and somatostatin on the release and synthesis of rGH in dispersed pituitary cells. Endocrinology 117:457–467Google Scholar
  13. Gick GG, Bancroft C (1987) Glucocorticoid stimulation of growth hormone messenger ribonucleic acid levels in GH3 cells is inhibited by calcium but not by somatostatin. Endocrinology 120:1986–1990Google Scholar
  14. Gick GG, Zeytin FN, Brazeau P, Ling NC, Esch FS, Bancroft C (1984) Growth hormone-releasing factor regulates growth hormone mRNA in primary cultures of rat pituitary cells. Proc Natl Acad Sci USA 81:1553–1555Google Scholar
  15. Grau EG, Nishioka RS, Young G, Bern HA (1985) Somatostatinlike immunoreactivity in the pituitary and brain of three teleost fish species: somatostatin as a potential regulator of prolactin cell function. Gen Comp Endocrinol 59:350–357Google Scholar
  16. Hirano T, Prunet P, Kawauchi H, Takahashi A, Ogasawara T, Kubota J, Nishioka RS, Bern HA, Takada K, Ishii S (1985) Development and validation of a salmon prolactin radioimmunoassay. Gen Comp Endocrinol 59:266–276Google Scholar
  17. Hobart P, Crawford R, Shen LP, Pictet R, Rutter WJ (1980) Cloning and sequence analysis of cDNAs encoding two distinct somatostatin precursors found in the endocrine pancreas of anglerfish. Nature 288:137–141Google Scholar
  18. Jones PM, Burrin JM, Ghatei MA, O'Halloran DJ, Legon S, Bloom SR (1990) The influence of thyroid hormone status on the hypothalamo-hypophyseal growth hormone axis. Endocrinology 126:1374–1379Google Scholar
  19. Karnik PS, Wolfe MM (1990) Somatostatin stimulates gastrin mRNA turnover in dog antral mucosa. J Biol Chem 265:2550–2555Google Scholar
  20. Karnik PS, Monahan SJ, Wolfe MM (1989) Inhibition of gastrin gene expression by somatostatin. J Clin Invest 83:367–372Google Scholar
  21. LeBail PY, Sumpter JP, Carragher JF, Mourot B, Niu PD, Weil C (1991) Development and validation of a highly sensitive radioimmunoassay for chinook salmon (Oncorhynchus tshawytscha) growth hormone. Gen Comp Endocrinol 83:75–85Google Scholar
  22. Lowe WL Jr, Schaffner AE, Roberts CT Jr, LeRoith D (1987) Developmental regulation of somatostatin gene expression in the brain is region specific. Mol Endocrinol 1:181–187Google Scholar
  23. Luo K, McKeown BA (1989) Immunohistochemical detection of a substance resembling growth hormone-releasing factor in the brain of the rainbow trout (Salmo gairdneri). Experientia 45:577–580Google Scholar
  24. Luo D, McKeown BA, Rivier J, Vale W (1990) In vitro responses of rainbow trout (Oncorhynchus mykiss) somatotrophs to carp growth hormone-releasing factor (GRF) and somatostatin. Gen Comp Endocrinol 80:288–298Google Scholar
  25. Marchant TA, Fraser RA, Andrews PC, Peter RE (1987) The influence of mammalian and teleost somatostatin on the secretion of growth hormone from goldfish (Carassius auratus L.) pituitary fragments in vitro. Regul Pept 17:41–52Google Scholar
  26. Martinoli MG, Pelletier G (1989) Thyroid and glucocorticoid hormone regulation of rat pituitary growth hormone messenger ribonucleic acid as revealed by in situ hybridization. Endocrinology 125:1246–1252Google Scholar
  27. Moons L, Cambre M, Marivoet S, Batten TFC, Vanderhaeghen J-J, Ollevier F, Vandesande F (1988) Peptidergic innervation of the adrenocorticotropic hormone (ACTH)-and growth hormone (GH)-producing cells in the pars distalis of the sea bass (Dicentrarchus labrax). Gen Comp Endocrinol 72:171–180Google Scholar
  28. Namba H, Morita S, Melmed S (1989) Insulin-like growth factor-I action on growth hormone secretion and messenger ribonucleic acid levels: interaction with somatostatin. Endocrinology 124:1794–1799Google Scholar
  29. Noe BD, Spiess J, Rivier JE, Vale W (1979) Isolation and characterization of somatostatin from anglerfish pancreatic islet. Endocrinology 105:1410–1415Google Scholar
  30. Olivereau M, Ollevier F, Vandesande F, Verdonck W (1984) Immunocytochemical identification of CRF-like and SRIF-like peptides in the brain and the pituitary of cyprinid fish. Cell Tissue Res 237:379–382Google Scholar
  31. Olivereau M, Olivereau J, Vandesande F (1990) Localization of growth hormone-releasing factor-like immunoreactivity in the hypothalamo-hypophysial system of some teleost species. Cell Tissue Res 259:73–80Google Scholar
  32. Pan JX, Lechan RM, Lin HD, Jackson IMD (1985) Immunoreactive neuronal pathways of growth hormone-releasing hormone (GRH) in the brain and pituitary of the teleost Gadus morhua. Cell Tissue Res 241:487–493Google Scholar
  33. Parker DB, Sherwood NM (1990) Evidence of a growth hormone-releasing hormone-like molecule in salmon brain, Oncorhynchus keta and O. kisutch. Gen Comp Endocrinol 79:95–102Google Scholar
  34. Patel YC, Srikant CB (1986) Somatostatin mediation of adenohypophysial secretion. Ann Rev Physiol 48:551–567Google Scholar
  35. Pérez-Sánchez J, Weil C, Le Bail P-Y (1992) Effects of human insulin-like growth factor-I on release of growth hormone by rainbow trout (Oncorhynchus mykiss) pituitary cells. J Exp Zool 262:287–290Google Scholar
  36. Peter RE, Nahorniak CS, Vale WW, Rivier JE (1984) Human pancreatic growth hormone-releasing factor (hpGRF) stimulates growth hormone release in goldfish. J Exp Zool 231:161–163Google Scholar
  37. Plisetskaya EM, Pollock HG, Rouse JB, Hamilton JW, Kimmel JR, Andrews PC, Gorbman A (1986) Characterization of coho salmon (Oncorhynchus kisutch) islet somatostatins. Gen Comp Endocrinol 63:252–263Google Scholar
  38. Rivas RJ, Nishioka RS, Bern HA (1986) In vitro effects of somatostatin and urotensin II on prolactin and growth hormone secretion in tilapia, Oreochromis mossambicus. Gen Comp Endocrinol 63:245–251Google Scholar
  39. Schally AV (1978) Aspects of hypothalamic regulation of the pituitary gland. Science 202:18–28Google Scholar
  40. Stachura ME (1977) Interaction of somatostatin inhibition and dibutyryl cyclic AMP or potassium stimulation of growth hormone release from perifused rat pituitaries. Endocrinology 101:1044–1053Google Scholar
  41. Stachura ME, Tyler JM, Farmer PK (1985) Human pancreatic growth hormone-releasing factor-44 differentially stimulates release of stored and newly synthesized rat growth hormone in vitro. Endocrinology 116:698–706Google Scholar
  42. Stachura ME, Tyler JM, Kent PG (1989) Pituitary immediate release pools of growth hormone and prolactin are preferentially refilled by new rather than stored hormone. Endocrinology 125:444–449Google Scholar
  43. Suzuki R, Kishida M, Hirano T (1990) Growth hormone secretion during longterm incubation of the pituitary of the Japanese eel, Anguilla japonica. Fish Physiol Biochem 8:159–165Google Scholar
  44. Suzuki R, Kaneko T, Hirano T (1991) Effects of osmotic pressure on prolactin and growth hormone secretion from organ-cultured eel pituitary. J Comp Physiol B 161:147–153Google Scholar
  45. Sweeting RM, McKeown BA (1986) Somatostatin reduces plasma growth hormone levels during seawater adaptation in coho salmon, Oncorhynchus kisutch. Can J Zool 64:2062–2063Google Scholar
  46. Tannenbaum GS, Guyda HJ, Posner BI (1983) Insulin-like growth factors: a role in growth hormone negative feedback and body weight regulation via brain. Science 220:77–79Google Scholar
  47. Vigh-Teichmann I, Vigh B, Korf H-W, Oksche A (1983) CSF-contacting and other somatostatin-immunoreactive neurons in the brains of Anguilla anguilla, Phoxinus phoxinus, and Salmo gairdneri (Teleostei). Cell Tissue Res 233:319–334Google Scholar
  48. Wigham T, Batten TFC (1984) In vitro effects of thyrotropin-releasing hormone and somatostatin on prolactin and growth hormone release by the pituitary of Poecilia latipinna. Gen Comp Endocrinol 55:444–449Google Scholar
  49. Yada T, Urano A, Hirano T (1991) Growth hormone and prolactin gene expression and release in the pituitary of rainbow trout in serum-free culture. Endocrinology 129:1183–1192Google Scholar
  50. Yamashita S, Melmed S (1987) Insulinlike growth factor I regulation of growth hormone gene transcription in primary rat pituitary cells. J Clin Invest 79:449–452Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Takashi Yada
    • 1
  • Tetsuya Hirano
    • 1
  1. 1.Ocean Research InstituteUniversity of TokyoTokyoJapan

Personalised recommendations