Asian-Australasian Journal of Animal Sciences

Asian Australasian Association of Animal Production Societies (아세아태평양축산학회)
권호 표지
DOI QR코드

DOI QR Code

Development and Characterization of a Novel Anti-idiotypic Monoclonal Antibody to Growth Hormone, Which Can Mimic Physiological Functions of Growth Hormone in Primary Porcine Hepatocytes

  • Lan, Hai-Nan (College of animal science and technology Jilin Agricultural University) ;
  • Jiang, Hai-Long (College of animal science and technology Jilin Agricultural University) ;
  • Li, Wei (State Key Laboratory of Animal Nutrition, China Agricultural University) ;
  • Wu, Tian-Cheng (College of animal science and technology Jilin Agricultural University) ;
  • Hong, Pan (College of animal science and technology Jilin Agricultural University) ;
  • Li, Yu Meng (College of animal science and technology Jilin Agricultural University) ;
  • Zhang, Hui (College of animal science and technology Jilin Agricultural University) ;
  • Cui, Huan-Zhong (College of animal science and technology Jilin Agricultural University) ;
  • Zheng, Xin (College of animal science and technology Jilin Agricultural University)
  • Received : 2014.08.06
  • Accepted : 2014.11.20
  • Published : 2015.04.01
Download PDF
⟨ Previous Next ⟩

Abstract

B-32 is one of a panel of monoclonal anti-idiotypic antibodies to growth hormone (GH) that we developed. To characterize and identify its potential role as a novel growth hormone receptor (GHR) agonist, we determined that B-32 behaved as a typical $Ab2{\beta}$ based on a series of enzyme-linked immunosorbent assay assays. The results of fluorescence-activated cell sorting, indirect immunofluorescence and competitive receptor binding assays demonstrated that B-32 specifically binds to the GHR expressed on target cells. Next, we examined the resulting signal transduction pathways triggered by this antibody in primary porcine hepatocytes. We found that B-32 can activate the GHR and Janus kinase (2)/signal transducers and activators of transcription (JAK2/STAT5) signalling pathways. The phosphorylation kinetics of JAK2/STAT5 induced by either GH or B-32 were analysed in dose-response and time course experiments. In addition, B32 could also stimulate porcine hepatocytes to secrete insulin-like growth factors-1. Our work indicates that a monoclonal anti-idiotypic antibody to GH (B-32) can serve as a GHR agonist or GH mimic and has application potential in domestic animal (pig) production.

Keywords

References

  1. Abdel-Meguid, S. S., H. S. Shieh, W. W. Smith, H. E. Dayriner, B. N. Violand, and L. A. Bentle. 1987. Three-dimensional structure of a genetically engineered variant of porcine growth hormone. Proc. Natl. Acad. Sci. USA. 84:6434-6437. https://doi.org/10.1073/pnas.84.18.6434
  2. Brameld, J. M., R. S. Gilmour, and P. J. Buttery. 1999. Glucose and amino acids interact with hormones to control expression of insulin-like growth factor-I and growth hormone receptor mRNA in cultured pig hepatocytes. J. Nutr. 129:1298-1306. https://doi.org/10.1093/jn/129.7.1298
  3. Brameld, J. M., P. A. Weller, J. C. Saunders, P. J. Buttery, and R. S. Gilmour. 1995. Hormonal control of insulin-like growth factor-I and growth hormone receptor mRNA expression by porcine hepatocytes in culture. J. Endocrinol. 146:239-245. https://doi.org/10.1677/joe.0.1460239
  4. Brooks, A. J. and M. J. Waters. 2010. The growth hormone receptor: mechanism of activation and clinical implications. Nat. Rev. Endocrinol. 6:515-525. https://doi.org/10.1038/nrendo.2010.123
  5. Caperna, T. J., A. E. Shannon, S. M. Poch, W. M. Garrett, and M. P. Richards. 2005. Hormonal regulation of leptin receptor expression in primary cultures of porcine hepatocytes. Domest. Anim. Endocrinol. 29:582-592. https://doi.org/10.1016/j.domaniend.2005.03.005
  6. Carlsson, L. M. S., D. L. Mortensen, B. C. Cunnungham, and R. G. Clark. 1994. A monoclonal antibody against the GH receptor stimulates growth in hypophysectomized rats. Program of the 76th Annual Meeting of The Endocrine Society. City, Country. 434.
  7. Chia, D. J., M. Ono, J. Woelfle, M. Schlesinger-Massart, H. Jiang, and P. Rotwein. 2006. Characterization of distinct Stat5b binding sites that mediate growth hormone-stimulated IGF-I gene transcription. J. Biol. Chem. 281:3190-3197. https://doi.org/10.1074/jbc.M510204200
  8. Conway-Campbell, B. L., J. W. Wooh, A. J. Brooks, D. Gordon, R. J. Brown, A. M. Lichanska, and M. J. Waters. 2007. Nuclear targeting of the growth hormone receptor results in dysregulation of cell proliferation and tumorigenesis. Proc. Natl. Acad. Sci. USA. 104:13331-13336. https://doi.org/10.1073/pnas.0600181104
  9. Elbashir, M. I., T. Brodin, B. Akerstrom, and J. Donner. 1990. Monoclonal antibodies to the pituitary growth-hormone receptor by the anti-idiotypic approach. Production and initial characterization. Biochem. J. 266:467-474. https://doi.org/10.1042/bj2660467
  10. Elsasser, T. H., C. J. Li, T. J. Caperna, S. Kahl, and W. F. Schmidt. 2007. Growth hormone (GH)-associated nitration of Janus kinase-2 at the 1007Y-1008Y epitope impedes phosphorylation at this site: mechanism for and impact of a GH, AKT, and nitric oxide synthase axis on GH signal transduction. Endocrinology 148:3792-3802. https://doi.org/10.1210/en.2006-1736
  11. Fernandez-Figares, I., A. E. Shannon, D. Wray-Cahen, and T. J. Caperna. 2004. The role of insulin, glucagon, dexamethasone, and leptin in the regulation of ketogenesis and glycogen storage in primary cultures of porcine hepatocytes prepared from 60 kg pigs. Domest. Anim. Endocrinol. 27:125-140. https://doi.org/10.1016/j.domaniend.2004.02.003
  12. Gardner, M. J., C. A. Morrison, L. Q. Stevenson, and D. J. Flint. 1990. Production of anti-idiotypic antisera to rat GH antibodies capable of binding to GH receptors and increasing body weight gain in hypophysectomized rats. J. Endocrinol. 125:53-59. https://doi.org/10.1677/joe.0.1250053
  13. Gebert, C. A., S. H. Park, and D. J. Waxman. 1999. Termination of growth hormone pulse-induced STAT5b signaling. Mol. Endocrinol. 13:38-56. https://doi.org/10.1210/mend.13.1.0235
  14. Herington, A. and P. Lobie. 2012. Signal transduction mechanisms underlying growth hormone receptor action. Open Endocrinol. J. 6:13-21. https://doi.org/10.2174/1874216501206010013
  15. Jerne, N. K. 1974. Towards a network theory of the immune system. Ann. Immunol. 125:373-389.
  16. Li, W., H. N. Lan, H. Liu, Z. Fu, Y. Yang, and W. W. Han, F. Guo, Y. Liu, H. Zhang, J. S. Liu, and X. Zheng. 2013. The activation and differential signalling of the growth hormone receptor induced by pGH or anti-idiotypic monoclonal antibodies in primary rat hepatocytes. Mol. Cell. Endocrinol. 376:51-59. https://doi.org/10.1016/j.mce.2013.06.008
  17. Mellado, M., J. M. Rodriguez-Frade, L. Kremer, C. von Kobbe, A. M. de Ana, I. Merida, and C. Martinez-A. 1997. Conformational changes required in the human growth hormone receptor for growth hormone signaling. J. Biol. Chem. 272:9189-9196. https://doi.org/10.1074/jbc.272.14.9189
  18. Milward, A., L. Metherell, M. Maamra, M. J. Barahona, I. R. Wilkinson, C. Camacho-Hubner, M. O. Savage, C. M. Bidlingmaier, A. J. L. Clark, R. J. M. Ross, and S. M. Webb. 2004. Growth hormone (GH) insensitivity syndrome due to a GH receptor truncated after Box1, resulting in isolated failure of STAT 5 signal transduction. J. Clin. Endocrinol. Metab. 89:1259-1266. https://doi.org/10.1210/jc.2003-031418
  19. Moller, N. and O. L. J. Jens. 2009. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr. Rev. 30:152-177. https://doi.org/10.1210/er.2008-0027
  20. Ramsay, T. G., M. P. Richards, C. J. Li, and T. J. Caperna. 2010. IGF-I mediated inhibition of leptin receptor expression in porcine hepatocytes. Comp. Biochem. Physiol B. Biochem. Mol. Biol. 155:43-48. https://doi.org/10.1016/j.cbpb.2009.09.007
  21. Rajput, Y. S., R. Sodhi, N. K. Verma. 2003. Anti-idiotypic Antibodies against bovine growth hormone. Asian Australas. J. Anim. Sci. 16:732-737. https://doi.org/10.5713/ajas.2003.732
  22. Roberge, S., B. N. Wilkie, and J. S. Walton. 1999. Anti-idiotypic responses of lactating cows immunized with monoclonal antibodies against bovine somatotropin. J. Dairy Sci. 82:1707-1715. https://doi.org/10.3168/jds.S0022-0302(99)75400-7
  23. Rowlinson, S. W., S. N. Behncken, J. E. Rowland, R. W. Clarkson, C. J. Strasburger, Z. Wu, W. Baumbach, and M. J. Waters. 1998. Activation of chimeric and full-length growth hormone receptors by growth hormone receptor monoclonal antibodies. A specific conformational change may be required for fulllength receptor signaling. J. Biol. Chem. 273:5307-5314. https://doi.org/10.1074/jbc.273.9.5307
  24. Sege, K. and P. A. Peterson. 1978. Use of anti-idiotypic antibodies as cell-surface receptor probes. Proc. Natl. Acad. Sci. USA. 75:2443-2447. https://doi.org/10.1073/pnas.75.5.2443
  25. Smit, L. S., D. J. Meyer, N. Billestrup, G. Norstedt, J. Schwartz, and C. Carter-Su. 1996. The role of the growth hormone (GH) receptor and JAK1 and JAK2 kinases in the activation of Stats 1, 3, and 5 by GH. Mol. Endocrinol. 10:519-533.
  26. Walsh, S. T., J. E. Sylvester, and A. A. Kossiakoff. 2004. The highand low-affinity receptor binding sites of growth hormone are allosterically coupled. Proc. Natl. Acad. Sci. USA. 101:17078-17083. https://doi.org/10.1073/pnas.0403336101
  27. Wan, Y., Y. Z. Zheng, J. M. Harris, R. Brown, and M. J. Waters. 2003. Epitope map for a growth hormone receptor agonist monoclonal antibody, MAb 263. Mol. Endocrinol. 17:2240-2250. https://doi.org/10.1210/me.2003-0162
  28. Wang, B. S., A. A. Lumanglas, C. A. Bona, and T. M. Moran. 1996. Promotion of animal growth with a monoclonal antibody specific to growth hormone receptor. Mol. Cell. Endocrinol 116:223-226. https://doi.org/10.1016/0303-7207(95)03718-7
  29. Wang, B. S., A. L. Lumanglas, C. A. Bona, and T. M. Moran. 1996. Functional characterization of monoclonal antibodies specific to growth hormone receptor. Mol. Immunol. 33:1197-1202. https://doi.org/10.1016/S0161-5890(96)00055-7
  30. Wang, B. S., R. J. Zhang, C. A. Bona, and T. M. Moran. 1994. Promotion of animal growth with a monoclonal anti-idiotypic specific to anti-porcine growth hormone antibody. Mol. Immunol. 31:651-656. https://doi.org/10.1016/0161-5890(94)90174-0
  31. Wu. Z., G. Lima, and C. J. Strasburger. 2010. Explore the mechanism of growth hormone signaling with growth hormone receptor monoclonal antibodies. Growth. Horm. IGF. Res. 20:S32-33.
  32. Zhu, T., E. L. K. Goh, R. Graichen, L. Ling, and P. E. Lobie. 2001. Signal transduction via the growth hormone receptor. Cell. Signal. 13:599-616. https://doi.org/10.1016/S0898-6568(01)00186-3

Cited by

  1. Preparation and Characterization of an Antibody Antagonist That Targets the Porcine Growth Hormone Receptor vol.29, pp.10, 2016, https://doi.org/10.5713/ajas.15.0892
  2. Development of a Novel, Anti-idiotypic Monoclonal Anti-prolactin Antibody That Mimics the Physiological Functions of Prolactin vol.29, pp.4, 2016, https://doi.org/10.5713/ajas.15.0541
  3. Mimetic peptide and special antibody: promising agents for optimizing hapten-analyzing systems vol.8, pp.12, 2016, https://doi.org/10.1039/C5AY02533H
  4. Growth Hormone Did Not Activate Its Intracellular Signaling Molecules in Rats’ Liver Hepatocytes During Early Life Period vol.16, pp.3, 2018, https://doi.org/10.5812/ijem.61385
  5. Porcine growth hormone induces the nuclear localization of porcine growth hormone receptor in vivo vol.31, pp.4, 2018, https://doi.org/10.5713/ajas.17.0585
  6. Zinc ions increase GH signaling ability through regulation of available plasma membrane‐localized GHR vol.234, pp.12, 2015, https://doi.org/10.1002/jcp.28908
  7. Preparation of a Growth Hormone Receptor/Prolactin Receptor Bispecific Antibody Antagonist Which Exhibited Anti-Cancer Activity vol.11, pp.None, 2015, https://doi.org/10.3389/fphar.2020.598423
  8. JAK2-STAT5 signaling is insensitive to porcine growth hormone (pGH) in hepatocytes of neonatal pig vol.24, pp.2, 2015, https://doi.org/10.1080/19768354.2020.1735518
  9. Agonist antibody discovery: Experimental, computational, and rational engineering approaches vol.27, pp.1, 2015, https://doi.org/10.1016/j.drudis.2021.09.008