Transgenic Research

, Volume 20, Issue 3, pp 513–521 | Cite as

GH overexpression causes muscle hypertrophy independent from local IGF-I in a zebrafish transgenic model

  • Rafael Y. Kuradomi
  • Márcio A. Figueiredo
  • Carlos F. C. Lanes
  • Carlos E. da Rosa
  • Daniela V. Almeida
  • Rodrigo Maggioni
  • Maeli D. P. Silva
  • Luis F. Marins
Original Paper

Abstract

The aim of the present study was to analyse the morphology of white skeletal muscle in males and females from the GH-transgenic zebrafish (Danio rerio) lineage F0104, comparing the expression of genes related to the somatotrophic axis and myogenesis. Histological analysis demonstrated that transgenic fish presented enhanced muscle hypertrophy when compared to non-transgenic fish, with transgenic females being more hypertrophic than transgenic males. The expression of genes related to muscle growth revealed that transgenic hypertrophy is independent from local induction of insulin-like growth factor 1 gene (igf1). In addition, transgenic males exhibited significant induction of myogenin gene (myog) expression, indicating that myog may mediate hypertrophic growth in zebrafish males overexpressing GH. Induction of the α-actin gene (acta1) in males, independently from transgenesis, also was observed. There were no significant differences in total protein content from the muscle. Our results show that muscle hypertrophy is independent from muscle igf1, and is likely to be a direct effect of excess circulating GH and/or IGF1 in this transgenic zebrafish lineage.

Keywords

Transgenic zebrafish Growth hormone Skeletal muscle Hypertrophy Myogenic factors 

References

  1. Acosta J, Carpio Y, Borroto I, González O, Estrada MP (2005) Myostatin gene silenced by RNAi show a zebrafish giant phenotype. J Biotechnol 119:324–331PubMedCrossRefGoogle Scholar
  2. Benito M, Valverde AM, Lorenzo M (1996) IGF-I: A mitogen also involved in differentiation processes in mammalian cells. Int J Biochem Cell Biol 28:499–510PubMedCrossRefGoogle Scholar
  3. Black BL, Olson EN (1998) Transcriptional control of muscle development by myocyte enhancer factor-2 (MEF2) proteins. Ann Rev Cell Dev Biol 14:167–196CrossRefGoogle Scholar
  4. Blackwell T, Weintraub H (1990) Differences and similarities in DNA-binding preferences of MyoD and E2A protein complexes revealed by binding site selection. Science 250:1104–1110PubMedCrossRefGoogle Scholar
  5. Butler AA, Le Roith D (2001) Control of growth by the somatotropic axis: growth hormone and the insulin-like growth factors have related and independent roles. Ann Rev Physiol 63:141–164CrossRefGoogle Scholar
  6. Canosa L, Chang JP, Peter RE (2007) Neuroendocrine control of growth hormone in fish. Gen Comp Endocrinol 151:1–26PubMedCrossRefGoogle Scholar
  7. Chatakondi N, Lovell RT, Duncan PL, Hayat M, Chen TT, Powers DA, Weete JD, Cummins K, Dunham RA (1995) Body composition of transgenic common carp, Cyprinus carpio, containing rainbow trout growth hormone gene. Aquaculture 138:99–109CrossRefGoogle Scholar
  8. Clark RP, Schuenke M, Keeton SM, Staron RS, Kopchick JJ (2006) Effects of growth hormone and insulin-like growth factor I on muscle in mouse models of human growth disorders. Horm Res 66:26–34PubMedCrossRefGoogle Scholar
  9. Cook JT, McNiven MA, Richardson GF, Sutterlin AM (2000) Growth rate, body composition and feed digestibility/conversion of growth enhanced Atlantic salmon (Salmo salar). Aquaculture 188:15–32CrossRefGoogle Scholar
  10. Czerwinski SM, Martin JM, Bechtel PJ (1994) Modulation of IGF mRNA abundance during stretch-induced skeletal muscle hypertrophy and regression. J Appl Physiol 76:2026–2030PubMedGoogle Scholar
  11. Devlin RH, Biagi CA, Yesaki TY (2004) Growth, viability and genetic characteristics of GH transgenic coho salmon strains. Aquaculture 236:607–632CrossRefGoogle Scholar
  12. Devlin RH, Sundström LF, Muir WM (2006) Interface of biotechnology and ecology for environmental risk assessments of transgenic fish. Trends Biotechnol 24:89–97PubMedCrossRefGoogle Scholar
  13. Du SJ, Gong ZY, Fletcher GL, Shears MA, King MJ, Idler DR, Hew CL (1992) Growth enhancement in transgenic Atlantic salmon by the use of an “all-fish” chimeric growth hormone gene construct. Biotechnology (N.Y.) 10:176–181CrossRefGoogle Scholar
  14. Dudley GA, Portanova R (1987) Histochemical characteristics of soleus muscle in hGH transgenic mice. Proc Soc Exp Biol Med 185:403–408PubMedGoogle Scholar
  15. Dunham RA, Chatakondi N, Nichols AJ, Kucuktas H, Chen TT, Powers DA, Weete JD, Cummins K, Lovell RT (2002) Effect of rainbow trout growth hormone complementary DNA on body shape, carcass yield, and carcass composition of F1 and F2 transgenic common carp (Cyprinus carpio). Mar Biotechnol 4:604–611PubMedCrossRefGoogle Scholar
  16. Eppler E, Caelers A, Shved N, Hwang G, Rahman AM, Maclean N, Zapf J, Reinecke M (2007) Insulin-like growth factor I (IGF-I) in a growth-enhanced transgenic (GH-overexpressing) bony fish, the tilapia (Oreochromis niloticus): indication for a higher impact of autocrine/paracrine than of endocrine IGF-I. Transgenic Res 16:479–489PubMedCrossRefGoogle Scholar
  17. Fauconneau B, Andre S, Chmaitilly J, Le Bail P, Krieg F, Kaushik SJ (1997) Control of skeletal muscle fibers and adipose cell size in the flesh of rainbow trout. J Fish Biol 50:296–314CrossRefGoogle Scholar
  18. Figueiredo MA, Lanes CFC, Almeida DV, Marins LF (2007a) Improving the production of transgenic fish germlines: in vivo evaluation of mosaicism in zebrafish (Danio rerio) using a green fluorescent protein (GFP) and growth hormone cDNA transgene co-injection strategy. Genet Mol Biol 30:31–36CrossRefGoogle Scholar
  19. Figueiredo MA, Lanes CFC, Almeida DV, Proietti MC, Marins LF (2007b) The effect of GH overexpression on GHR and IGF-I gene regulation in different genotypes of GH-transgenic zebrafish. Comp Biochem Phys D 2:228–233Google Scholar
  20. Florini JR, Ewton DZ, Coolican SA (1996) Growth hormone and the insulin-like growth factor system in myogenesis. Endocr Rev 17:481–517PubMedGoogle Scholar
  21. Fu C, Cu Y, Hung SSO, Zhu Z (1998) Growth and feed utilization by F4 human growth hormone transgenic carp fed diets with different protein levels. J Fish Biol 53:115–129Google Scholar
  22. Hasty P, Bradley A, Morris JH, Edmondson DG, Venuti JM, Olson EN, Klein WH (1993) Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene. Nature 364:501–506PubMedCrossRefGoogle Scholar
  23. Hikida RS, Knapp JR, Chen WY, Gozdanovic JA, Kopchick JJ (1995) Effects of bovine growth hormone analogs on mouse skeletal muscle structure. Growth Dev Aging 59:121–128PubMedGoogle Scholar
  24. Hill JA, Kiessling A, Devlin RH (2000) Coho salmon (Oncorhynchus kisutch) transgenic for a growth hormone gene construct exhibit increased rates of muscle hyperplasia and detectable levels of differential gene expression. Can J Fish Aquat Sci 57:939–950CrossRefGoogle Scholar
  25. Hong MH, Sun H, Jin CH, Chapman M, Hu J, Chang W, Burnett K, Rosen J, Negro-Vilar A, Miner JN (2008) Cell-specific activation of the human skeletal α-actin by androgens. Endocrinology 149:1103–1112PubMedCrossRefGoogle Scholar
  26. Ihle JN (1996) STATs: Signal transducers and activators of transcription. Cell 84:331–334PubMedCrossRefGoogle Scholar
  27. Jansson JO, Edén S, Isaksson O (1985) Sexual dimorphism in the control of growth hormone secretion. Endocr Rev 6:128–150PubMedCrossRefGoogle Scholar
  28. Johansen KA, Overturf K (2005) Quantitative expression analysis of genes affecting muscle growth during development of rainbow trout (Oncorhynchus mykiss). Mar Biotechnol 7:576–587PubMedCrossRefGoogle Scholar
  29. Johnston IA (1999) Muscle development and growth: potential implication for flesh quality in fish. Aquaculture 177:99–115CrossRefGoogle Scholar
  30. Kajimura S, Uchida K, Yada T, Riley LG, Byatt JC, Collier RJ, Ainda K, Hirano T, Grau EG (2001) Stimulation of insulin-like growth factor-I production by recombinant bovine growth hormone in Mozambique tilapia, Oreochromis mossambicus. Fish Physiol Biochem 25:221–230CrossRefGoogle Scholar
  31. Koumans JTM, Akster HA (1995) Myogenic cells in development and growth of fish. Comp Biochem Phys A 110:3–20CrossRefGoogle Scholar
  32. Lassar A, Buskin JN, Lockshon D, Davis RL, Apone S, Hauschka SD, Weintraub H (1989) MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer. Cell 58:823–831PubMedCrossRefGoogle Scholar
  33. Le Roith D, Scavo L, Buttle A (2001) What is the role of circulating IGF-I? Trends Endocrinol Metab 12:48–52PubMedCrossRefGoogle Scholar
  34. Marins LF, Iyengar A, Maclean N, Levy JA, Sohm F (2002) Simultaneous overexpression of GH and STAT5b genes inhibits the STAT5 signalling pathway in tilapia (Oreochromis niloticus) embryos. Genet Mol Biol 23:293–298CrossRefGoogle Scholar
  35. McPherron AC, Lawler AM, Lee SJ (1997) Regulation of skeletal muscle mass in mice by a new TGF-β superfamily member. Nature 387:83–90PubMedCrossRefGoogle Scholar
  36. Moriyama S, Ayson FG, Kawauchi H (2000) Growth regulation by insulin-like growth factor-I in fish. Biosci Biotech Bioch 64:1553–1562CrossRefGoogle Scholar
  37. Murre C, McCaw PS, Vaessin H, Caudy M, Jan LY, Jan YN, Cabrera CV, Buskin JN, Hauschka SD, Lassar AB (1989) Interactions between heterologous helix–loop–helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58:537–544PubMedCrossRefGoogle Scholar
  38. Nabeshima Y, Hanaoka K, Hayasaka M, Esumi E, Li S, Nonaka I, Nabeshima Y (1993) Myogenin gene disruption results in perinatal lethality because of severe muscle defect. Nature 364:532–535PubMedCrossRefGoogle Scholar
  39. Nam YK, Noh JK, Cho YS, Cho HJ, Cho KN, Kim CG, Kim DS (2001) Dramatically accelerated growth and extraordinary gigantism of transgenic mud loach Misgurnus mizolepis. Transgenic Res 10:353–362PubMedCrossRefGoogle Scholar
  40. Nordgarden U, Fjelldal PG, Hansen T, Björnsson BT, Wargelius A (2006) Growth hormone and insulin-like growth factor-I act together and independently when regulating growth in vertebral and muscle tissue of atlantic salmon postsmolts. Gen Comp Endocrinol 149:253–260PubMedCrossRefGoogle Scholar
  41. Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST©) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30:e36PubMedCrossRefGoogle Scholar
  42. Pitkänen TI, Xie SQ, Krasnov A, Mason PS, Mölsä H, Stickland NC (2001) Changes in tissue cellularity are associated with growth enhancement in genetically modified Arctic char (Salvelinus alpinus L.) carrying recombinant growth hormone gene. Mar Biotechnol 3:188–197PubMedCrossRefGoogle Scholar
  43. Pownall ME, Gustafsson MK, Emerson CP (2002) Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos. Ann Rev Cell Dev Biol 18:747–783CrossRefGoogle Scholar
  44. Price NT, Kimball SR, Jefferson LS, Proud CG (1996) Cloning of cDNA for the gamma-subunit of mammalian translation initiation factor 2B, the guanine nucleotide-exchange factor for eukaryotic initiation factor 2. Biochem J 318:631–636PubMedGoogle Scholar
  45. Rabinovsky ED, Gelir E, Gelir S, Lui H, Kattash M, Demayo FJ, Shenaq SM, Schwartz RJ (2002) Targeted expression of IGF-1 transgene to skeletal muscle accelerates muscle and motor neuron regeneration. FASEB J 17:53–55PubMedGoogle Scholar
  46. Rahman MA, Mak R, Ayad H, Smith A, Maclean N (1998) Expression of a novel piscine growth hormone gene results in growth enhancement in transgenic tilapia (Oreochromis niloticus). Transgenic Res 7:357–369PubMedCrossRefGoogle Scholar
  47. Rahman MA, Ronyai A, Engidaw BZ, Jauncey K, Hwang GL, Smith A, Roderick E, Penman D, Varadi L, Maclean N (2001) Growth and nutritional trials on transgenic Nile tilapia containing an exogenous fish growth hormone gene. J Fish Biol 59:62–78CrossRefGoogle Scholar
  48. Reinecke M, Björnsson BT, Dickhoff WW, McCormick SD, Navarro I, Power DM, Gutiérrez J (2005) Growth hormone and insulin-like growth factors in fish: where we are and where to go. Gen Comp Endocrinol 42:20–24CrossRefGoogle Scholar
  49. Rosa CE, Figueiredo MA, Lanes CFC, Almeida DV, Monserrat JM, Marins LF (2008) Metabolic rate and reactive oxygen species production in different genotypes of GH-transgenic zebrafish. Comp Biochem Phys B 149:209–214CrossRefGoogle Scholar
  50. Rowlerson A, Veggetti A (2001) Cellular mechanisms of post-embryonic muscle growth in aquaculture species. In: Johnston IA (ed) Muscle development and growth. Academic Press, London, pp 103–140CrossRefGoogle Scholar
  51. Schindler C, Darnell JE (1995) Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Ann Rev Biochem 64:621–651PubMedCrossRefGoogle Scholar
  52. Shavlakadze T, Winn N, Rosenthal N, Grounds MD (2005) Reconciling data from transgenic mice that overexpress IGF-I specifically in skeletal muscle. Growth Horm IGF Res 15:4–18PubMedCrossRefGoogle Scholar
  53. Sokal RR, Rohlf FJ (1995) Biometry, 3rd edn. WH Freeman, New YorkGoogle Scholar
  54. Sotiropoulos A, Ohanna M, Kedzia C, Menon RK, Kopchick JJ, Kelly PA, Pende M (2006) Growth hormone promotes skeletal muscle cell fusion independent of insulin-like growth factor 1 up-regulation. Proc Natl Acad Sci USA 103:7315–7320PubMedCrossRefGoogle Scholar
  55. Spence R, Fatema MK, Ellis S, Ahmed ZF, Smith C (2007) The diet, growth and recruitment of wild zebrafish (Danio rerio) in Bangladesh. J Fish Biol 71:304–309CrossRefGoogle Scholar
  56. Stewart CE, Rotwein P (1996) Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. Physiol Rev 76:1005–1026PubMedGoogle Scholar
  57. Studzinski AL, Almeida DV, Lanes CF, Figueiredo MA, Marins LF (2009) SOCS1 and SOCS3 are the main negative modulators of the somatotrophic axis in liver of homozygous GH-transgenic zebrafish (Danio rerio). Gen Comp Endocrinol 161:67–72PubMedCrossRefGoogle Scholar
  58. Uchida K, Kajimura S, Riley LG, Hirano T, Ainda K, Grau EG (2003) Effects of fasting on growth hormone/insulin-like growth factor I axis in the tilapia, Oreochromis mossambicus. Comp Biochem Phys A 134:429–433CrossRefGoogle Scholar
  59. Valente LMP, Rocha E, Gomes EFS, Silva MW, Oliveira MH, Monteiro RAF, Fauconneau B (1999) Growth dynamics of white and red muscle fibers in fast and slow-growing strains of rainbow trout. J Fish Biol 55:675–691CrossRefGoogle Scholar
  60. Vlahopoulos S, Zimmer WE, Jenster G, Belaguli NS, Balk SP, Brinkmann AO, Lanz RB, Zoumpourlis VC, Schwartz RJ (2005) Recruitment of the androgen receptor via serum response factor facilitates expression of a myogenic gene. J Biol Chem 280:7786–7792PubMedCrossRefGoogle Scholar
  61. Watabe S (1999) Myogenic regulatory factors and muscle differentiation during ontogeny in fish. J Fish Biol 55:1–18CrossRefGoogle Scholar
  62. Watabe S (2001) Myogenic regulatory factors. In: Johnston IA (ed) Muscle development and growth. Academic Press, London, pp 19–41CrossRefGoogle Scholar
  63. Waters MJ, Hoang HN, Fairlie DP, Pelekanos RA, Brown RJ (2006) New insights into growth hormone action. J Mol Endocrinol 36:1–7PubMedCrossRefGoogle Scholar
  64. Weatherley AH, Gill H (1982) Influence of bovine growth hormone on the growth dynamics of mosaic muscle in relation to somatic growth of rainbow trout O. mykiss. J Fish Biol 20:165–172CrossRefGoogle Scholar
  65. Weatherley A, Gill H, Lobo AF (1988) Recruitment and maximal diameter of axial muscle fibers in the teleosts and their relationship to somatic growth and ultimate size. J Fish Biol 33:851–859CrossRefGoogle Scholar
  66. Westerfield M (1995) The zebrafish book: a guide for the laboratory use of zebrafish Danio rerio, 3rd edn. University of Oregon Press, EugeneGoogle Scholar
  67. Wood AW, Duan C, Bern HA (2005) Insulin-like growth factor signaling in fish. Int Rev Cytol 243:215–285PubMedCrossRefGoogle Scholar
  68. Yakar S, Liu J, Stannard B, Butler A, Accili D, Sauer B, Le Roith D (1999) Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci USA 96:7324–7329PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Rafael Y. Kuradomi
    • 3
  • Márcio A. Figueiredo
    • 3
  • Carlos F. C. Lanes
    • 4
  • Carlos E. da Rosa
    • 1
  • Daniela V. Almeida
    • 2
  • Rodrigo Maggioni
    • 5
  • Maeli D. P. Silva
    • 6
  • Luis F. Marins
    • 1
    • 2
    • 3
  1. 1.Instituto de Ciências BiológicasUniversidade Federal do Rio Grande, FURGRio GrandeBrazil
  2. 2.Programa de Pós-Graduação em Ciências Fisiológicas, Fisiologia Animal ComparadaInstituto de Ciências Biológicas, FURGRio GrandeBrazil
  3. 3.Programa de Pós-Graduação em Aqüicultura, Instituto de Oceanografia, FURGRio GrandeBrazil
  4. 4.Faculty of Biosciences and AquacultureBodø University CollegeBodøNorway
  5. 5.Instituto de Ciências do MarUniversidade Federal do Ceará, UFCFortalezaBrazil
  6. 6.Departamento de Morfologia, Instituto de BiociênciasUniversidade Estadual Paulista, UNESPBotucatuBrazil

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