Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 4/1/2003
Publication Date: 5/1/2003
Citation: Khan, A.S., Fiorotto, M.L., Cummings, K.K., Pope, M., Brown, P.A., Draghia-Akli, R. 2003. Maternal GHRH plasmid administration changes pituitary cell lineage and improves progeny growth of pigs [abstract]. Molecular Therapy, The American Society of Gene Therapy. Part 2, 7(5):S380. Interpretive Summary: Not Necessary for an Abstract
Technical Abstract: Recently, we demonstrated that delivery of a plasmid, followed by electroporation, is an efficient strategy for long-term enhancement of GHRH production. Previous studies from our laboratory have shown that administration of a myogenic plasmid that expresses protease-resistant growth hormone-releasing hormone (HV-GHRH)to pregnant rat dams augmented long-term growth in first-generation progeny. In the present study, gilts were injected intramuscularly at day 85 of gestation with 0, 0.1, 0.5, 1, and 5 mg followed by electroporation of the HV-GHRH-expressing plasmid. Piglets were weighed, bled periodically and grown to finishing weight of 100 kg. The average birth weights of piglets born to gilts that had received the 5 mg dose of plasmid were significantly (P<0.025) higher than birth weights of piglets born to control gilts or gilts injected with 0.1 or 0.5 mg. Piglets born to the 1 mg gilts were larger at birth, but the difference was not statistically significant due to small litter sizes. Piglets from GHRH plasmid-treated gilts also had higher levels of circulating GHRH at birth relative to controls. IGF-I levels were significantly increased in the 5 mg group beginning at 21 days of age compared with control animals (P<0.05). Immunohistochemical analysis revealed that pituitaries from the 5 mg group contained a significantly increased number of somatotrophs and lactotrophs from birth to 100 kg. Samples from injected gilts and livers from piglets were analyzed by PCR and were negative for the presence of the plasmid. This study confirms our previous observations that increased maternal GHRH production results in enhanced intergenerational growth, and that the magnitude of the response is dose dependent. A single treatment with a plasmid expressing HV-GHRH to a pregnant animal produces effects similar to those exerted from multiple injections of GHRH or GH to the offspring. The similarity of the response across species as well as other evidence suggests that the effect is likely exerted as a fundamental component of gestational and developmental physiology. Plasmid Average Total Birth Weaning 130 d dose litter pig weight weight weight (mg) size studied (kg) (kg) (kg) 0 9 12 1.53 +/- 0.08 6.83 +/- 0.37 93.7 +/- 1.54 0.1 12 17 1.55 +/- 0.04 6.18 +/- 0.23 94.3 +/- 1.38 0.5 8 10 1.43 +/- 0.07 5.57 +/- 0.25 93.2 +/- 1.41 1.0 4 5 1.72 +/- 0.14 7.84 +/- 0.78 96.7 +/- 3.39 1.5 7 8 1.73 +/- 0.07 7.86 +/- 0.20 103.9 +/- 1.39 All values depicted as mean +/- SE.