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Title: A comparison of the growth responses following intramuscular GHRH plasmid administration versus daily growth hormone injections in young pigs

Author
item KHAN, AMIR - Inovio Pharmaceuticals, Inc
item DRAGHIA-AKLI, RUXANDRA - Inovio Pharmaceuticals, Inc
item SHYPAILO, ROMAN - Children'S Nutrition Research Center (CNRC)
item ELLIS, KENNETH - Children'S Nutrition Research Center (CNRC)
item MERSMANN, HARRY - Children'S Nutrition Research Center (CNRC)
item FIOROTTO, MARTA - Children'S Nutrition Research Center (CNRC)

Submitted to: Molecular Therapy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/5/2009
Publication Date: 10/6/2009
Citation: Khan, A.S., Draghia-Akli-R., Shypailo, R.J., Ellis, K.I., Mersmann, H., Fiorotto, M.L. 2010. A comparison of the growth responses following intramuscular GHRH plasmid administration versus daily growth hormone injections in young pigs. Molecular Therapy. 18(2):327-333.

Interpretive Summary: Growth hormone (GH) improves growth and body composition in humans and animals, but it requires frequent (daily) injections, and when used long term can have undesirable side effects such as joint stiffness or muscle and joint pain. An alternative is to use substances that stimulate the body to release more of its own GH. One such substance, growth hormone releasing hormone (GHRH), is produced by the body and has very few side effects. Our goal was to find the dose of plasmid (pGHRH) that would optimally increase body weight and lean mass, and to compare the pGHRH growth response with the routine of daily GH injections. The GH and pGHRH piglets gained more weight than controls, due mostly to increases in lean mass. Body fat increases were similar for all of the piglets regardless of treatment. Weight gains for the GH and pGHRH piglets were similar during the first 6 weeks, but over the last 10 days, only those piglets that had received the higher dose of pGHRH maintained the higher growth rates, similar to those of piglets receiving the daily GH injections. These results show that our method of pGHRH administration is effective in promoting growth, while avoiding the need for frequent injections and side-effects of GH. Such results may have the potential of being utilized in a health setting.

Technical Abstract: The efficacy of daily porcine growth hormone (GH) injections versus plasmid-driven porcine GH-releasing hormone (pGHRH) production to promote growth was assessed. Ten-day-old piglets were injected intramuscularly with 0.1, 1, or 3 mg pGHRH, or a control plasmid followed by electroporation. Plasmid constructs were driven by a synthetic muscle-specific promoter. A fifth group received daily injections of GH [0.15 mg/(kg·day)]. Control and pGHRH-treated pigs were pair-fed to GH-treated pigs. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). Weight gains of GH- and pGHRH-treated pigs were greater than of controls (P < 0.001) due to greater lean mass accretion; fat accretion was similar across all treatments. Weight gain of pGHRH- and GH-treated pigs was similar for 6 weeks, but over the final 10 days, only pigs administered the highest plasmid dose maintained higher growth rates. Serum insulin-like growth factor-I (IGF-I) levels were two- to threefold higher in GH- and pGHRH-treated pigs than in controls after 4 weeks (P = 0.05), but subsequently decreased to control levels in the pGHRH-treated group. Organ weights were greater in GH- than pGHRH-treated and control piglets (P < 0.02). These results demonstrate that pGHRH transfer is effective for promoting growth and avoids the need for the frequent injections necessitated with peptide hormone use.