Human growth hormone and insulin, from tissue extracts to recombinant DNA technology, their biosimilars and analogues in treatment of Endocrine Disorders
Main Article Content
Abstract
Forty years ago, recombinant DNA technology caused a revolution in the way growth disorders and diabetes could be treated. Bacteria or human cells were modified so as to be able to produce human hormones instead of relying on cadaveric material in the case of growth disorders and porcine insulin in the case of diabetics. The new technology also removed the risk of contracted hepatitis or fatal Creutzfeldt Jacob disease.
A signal peptide was used to transport the new protein into the periplasmic space giving rise to an exact, correctly folded version of monomeric human growth hormone.
More eligible patients could be treated, resulting not only in a large number of clinical trials. Daily tiny subcutaneous injections were found to be much more effective than twice or thrice weekly in the treatment of children and adults,
The progress for recombinant human insulin turned out to be somewhat different. Insulin is a more complicated protein, with an Alpha and Beta chain joined by two disulphide bridges, but is produced in the human pancreas as a single chain, proinsulin, the C peptide is removed to make the active molecule.
Recombinant insulin development was in a way the opposite to growth hormone since human insulin acts faster than porcine. Short fast and long-acting analogues have been developed all to improve the treatment regimens for both type 1 and type 2 diabetics,
A similar development is now taking place in the growth hormone field. Depot preparations for weekly administration are under development to achieve better compliance. One recently approved depot uses an analogue, modified in one amino acid of the peptide chain to permit acylation and albumin binding. In a way this is a retrograde step and it remains to be seen if the patient’s growth and metabolic responses are comparable to the daily administration of tiny amount of recombinant natural sequence hormone over several years of treatment.
Article Details
How to Cite
FRYKLUND, Linda.
Human growth hormone and insulin, from tissue extracts to recombinant DNA technology, their biosimilars and analogues in treatment of Endocrine Disorders.
Medical Research Archives, [S.l.], v. 11, n. 3, mar. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3681>. Date accessed: 04 dec. 2024.
doi: https://doi.org/10.18103/mra.v11i3.3681.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Riggs AD. Making, Cloning, and the Expression of Human Insulin Genes in Bacteria: The Path to Humulin. Endocr Rev. 2021 May 25;42(3):374-380. doi: 10.1210/endrev/bnaa029.
4. Farrugia A. Plasma for fractionation: safety and quality issues. Haemophilia. 2004 Jul;10(4):334-40. doi: 10.1111/j.1365-2516.2004.00911.x. PMID: 15230946.
5. Isfordink CJ, van Erpecum KJ, van der Valk M, Mauser-Bunschoten EP, Makris M. Viral hepatitis in haemophilia: historical perspective and current management. Br J Haematol. 2021 Oct;195(2):174-185. doi: 10.1111/bjh.17438. Epub 2021 May 6.PMID: 33955555.
6. Collett-Solberg PF, Ambler G, Backeljauw PF, Bidlingmaier M, Biller BMK, Boguszewski MCS, Cheung PT, Choong CSY, Cohen LE, Cohen P, Dauber A, Deal CL, Gong C, Hasegawa Y, Hoffman AR, Hofman PL, Horikawa R, Jorge AAL, Juul A, Kamenický P, Khadilkar V, Kopchick JJ, Kriström B, Lopes MLA, Luo X, Miller BS, Misra M, Netchine I, Radovick S, Ranke MB, Rogol AD, Rosenfeld RG, Saenger P, Wit JM, Woelfle J. Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective. Horm Res Paediatr. 2019;92(1):1-14. doi: 10.1159/000502231. Epub 2019 Sep 12. PMID: 31514194; PMCID: PMC6979443.
7. Roos P, Fevold Hr, Gemzell Ca. Preparation Of Human Growth Hormone By Gel Filtration. Biochim Biophys Acta. 1963 Aug 13;74:525-31. doi: 10.1016/0006-3002(63)91395-7. PMID: 14071596
8. Holmström B, Fhölenhag K. Characterization of human growth hormone preparations used for the treatment of pituitary dwarfism: a comparison of concurrently used batches. J Clin Endocrinol Metab. 1975 May;40(5):856-62. doi: 10.1210/jcem-40-5-856. PMID: 1127091
9. Billette de Villemeur T and Pradel A. Iatrogenic Creutzfeldt-Jakob disease. Lessons from cases secondary to extracted growth hormone in France, Transfus Clin Biol. 1994;1(5):333-7.
10. Rudge P 1, Jaunmuktane Z, Adlard P, Bjurstrom N, Caine D, Lowe J, NorsworthyP, Hummerich P Druyeh R, Wadsworth JDF, Brandner S, Hyare H, Mead S, Collinge J. Brain 2015 Nov;138(Pt 11):3386-99.doi: 10.1093/brain/awv235. Epub 2015 Aug 11.
11. Brostedt P, Roos P. Isolation of dimeric forms of human pituitary growth hormone. Prep Biochem. 1989;19(3):217-29. doi: 10.1080/10826068908544912. PMID: 2616540.
12. Purrello F, Vigneri R, Belfiore A, Pezzino V, Squatrito S, Polosa P. High incidence of anti-GH antibodies in subjects treated with the GH clinical preparation available in Italy. J Endocrinol Invest. 1980 Jul-Sep;3(3):313-5. doi: 10.1007/BF03348283. PMID: 7430559.
13. Li, C.H., Human Pituitary Growth Hormone .19. Primary Structure Of Hormone, Archives Of Biochemistry And Biophysics 133: 70 (1969).
14. de Vos AM, Ultsch M, Kossiakoff AA. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science. 1992 Jan 17;255(5042):306-12. doi: 10.1126/science.1549776. PMID: 1549776.
15. Ricci MS, Brems DN. Common structural stability properties of 4-helical bundle cytokines: possible physiological and pharmaceutical consequences. Curr Pharm Des. 2004;10(31):3901-11. doi: 10.2174/1381612043382611. PMID: 15579079.
16. Somers W, Ultsch M, De Vos AM, Kossiakoff AA. The X-ray structure of a growth hormone-prolactin receptor complex. Nature. 1994 Dec 1;372(6505):478-81. doi: 10.1038/372478a0. PMID: 7984244.
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