|Khan, Amir - ADVISYS, INC.|
|Cummings, Kathleen - ADVISYS, INC.|
|Pope, Melissa - ADVISYS, INC.|
|Brown, Patricia - ADVISYS, INC.|
|Draghia-Akli, Ruxandra - ADVISYS, INC.|
Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 29, 2003
Publication Date: April 1, 2003
Citation: Khan, A.S., Fiorotto, M.L., Cummings, K.K., Pope, M.A., Brown, P.A., Draghia-Akli, R. 2003. Maternal GHRH plasmid administration changes pituitary cell lineage and improves progeny growth of pigs. American Journal of Physiology, Endocrinology and Metabolism. 285(1):E224-E231. Interpretive Summary: We have developed a genetic approach to stimulate the growth of lean body mass in pigs. This involves injecting into muscle the gene that encodes a modified growth hormone-releasing hormone (GHRH), which works by increasing the amount of its own, natural growth hormone that the animal makes. We administered to sows at 85 days of pregnancy one of 5 different doses of the modified GHRH gene. At birth, the piglets of the sows that received the highest dose were heavier, and reached 100 kg 9 days before the other piglets. We also showed that the pituitaries of these offspring had higher numbers of those cells that produce growth hormone and prolactin, even though the piglets themselves had not been treated. These findings suggest that maternal GHRH levels, whether artificially or naturally altered, can impact the long-term growth of the subsequent generation.
Technical Abstract: Previous studies from our laboratory have demonstrated that administration of a myogenic plasmid that encodes a 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 intra-muscularly at "day 85" of gestation with 0, 0.1, 0.5, 1, or 5 mg of the HV-GHRH-expressing plasmid and were then electroporated. Piglets were weighed and bled periodically from birth to 100 kg. Piglets from gilts treated with 1 and 5 mg of HV-GHRH plasmid were larger at birth and weaning compared with controls. These two groups reached 100 kg 9 days earlier than the other groups. GHRH levels were increased at birth in piglets from treated gilts. IGF-I levels were significantly increased in the 5-mg group beginning at 21 days of age compared with controls. Pituitaries from the 5-mg group contained a significantly increased number of somatotrophs and lactotrophs from birth to 100 kg. This study confirms that enhanced maternal GHRH production results in intergenerational growth augmentation and that the magnitude of the response is dose dependent. The similarity of the response across species suggests that the effect is likely exerted as a fundamental component of gestational and developmental physiology.