Effects of plasmid-mediated growth hormone releasing hormone supplementation in young,healthy Beagle dogs

Our study focused on the evaluation of the pharmacological and toxicological effects of plasmid-mediated GHRH supplementation with electroporation in normal adult dogs over a 180-d period. Twenty-eight dogs (< 2 yr of age) were randomized to four groups. Three groups (four dogs/sex for each group) were treated with ascending doses of GHRH-expressing plasmid: 0.2, 0.6, and 1 mg. One group (two dogs of each sex) served as the control. Clinical observations and body weights were recorded. Hematological, serum biochemical, and urine analyses were performed. Serum IGF-I, ACTH, and insulin were determined. Necropsies were performed on d 93 and 180; organs were weighed and tissues were fixed and processed for light microscopy. Selected tissues were used to assess plasmid biodistribution on d 93. At all doses, plasmid GHRH caused increased weight gain (P < 0.001), without organomegaly. Serum glucose and insulin in fasted dogs remained within normal ranges at all time points. Adrenocorticotropic hormone was normal in all groups. Significant increases in number of red blood cells, hematocrit, and hemoglobin (P < 0.01) were observed. In conclusion, our study shows that plasmid-mediated GHRH supplementation is safe in electroporated doses up to 1.0 mg in young healthy dogs.