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Myogenic expression of an injectable protease-resistant growth hormone–releasing hormone augments long-term growth in pigs

Nature Biotechnology volume 17, pages 1179–1183 (1999)Cite this article

Abstract

Ectopic expression of a new serum protease-resistant porcine growth hormone–releasing hormone, directed by an injectable muscle-specific synthetic promoter plasmid vector (pSP-HV-GHRH), elicits growth in pigs. A single 10 mg intramuscular injection of pSP-HV-GHRH DNA followed by electroporation in three-week-old piglets elevated serum GHRH levels by twofold to fourfold, enhanced growth hormone secretion, and increased serum insulin-like growth factor-I by threefold to sixfold over control pigs. After 65 days the average body weight of the pigs injected with pSP-HV-GHRH was ~37% greater than the placebo-injected controls and resulted in a significant reduction in serum urea concentration, indicating a decrease in amino acid catabolism. Evaluation of body composition indicated a uniform increase in mass, with no organomegaly or associated pathology.

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Figure 1: GHRH superactive analogs increase GH secretagogue activity and stability.
Figure 2: Single injections of GHRH myogenic expression vectors in vivo increases porcine GHRH, GH, and IGF-I serum levels over two months.
Figure 3: Myogenic GHRH expression vectors enhance pig growth.

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Acknowledgements

We thank Jim Cunningham, Frankie Biggs, Craig Stubblefield, and MichaelStubblefield for excellent care of the animals; Dr. Harry Mersmann, RomanShipaylo, and Dr. Ken Ellis for the body composition measurements; CharlesMcDonald and Dr. Richard Cook for the synthesis of the HV-GHRH polypeptide;Jana Peters for the GH assays; and Dr. Craig Delaughter for carefully reviewing thismanuscript. We acknowledge support for this study from Applied VeterinarySystems Inc. (Houston, TX), The Texas Advanced Technology Program, and theNational Space Biological Research Institute (NASA), the US Department ofAgriculture, Agricultural Research Service under Cooperative Agreement number58-6250-6001. The contents of this publication do not necessarily reflect the viewsor policies of the US Department of Agriculture nor does mention of trade names orcommercial products or organizations imply endorsements by the US government.

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Authors and Affiliations

  1. Department of Cell Biology, Baylor College of Medicine, Houston, 77030, TX

    Ruxandra Draghia-Akli, Leigh Anne Hill, P. Brandon Malone & Robert J. Schwartz

  2. Department of Pediatrics, USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, 77030, TX

    Marta L. Fiorotto

  3. The Pennsylvania State University, University Park, 16802, PA

    Daniel R. Deaver

  4. Applied Veterinary Systems, Houston, 77030, TX

    Ruxandra Draghia-Akli, Leigh Anne Hill, P. Brandon Malone & Robert J. Schwartz

  5. National Space Biological Research Institute, Houston, 77030, TX

    Robert J. Schwartz

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  1. Ruxandra Draghia-Akli
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Correspondence to Ruxandra Draghia-Akli or Robert J. Schwartz.

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Draghia-Akli, R., Fiorotto, M., Hill, L. et al. Myogenic expression of an injectable protease-resistant growth hormone–releasing hormone augments long-term growth in pigs. Nat Biotechnol 17, 1179–1183 (1999). https://doi.org/10.1038/70718

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