Previous studies from our laboratory have demonstrated that administration of a myogenic plasmid that encodes a proteaseresistant 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, 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. growth hormone-releasing hormone; insulin-like growth factor I; electroporation IN HEALTHY ADULT MAMMALS, growth hormone (GH) is released in a regulated, distinctively pulsatile pattern. This phenomenon is under the control of the hypothalamic hormones, growth hormone-releasing hormone (GHRH) and somatostatin. This pulsatile pattern of GH secretion is fundamental to its biological activity (1) and is required for its physiological effects at the peripheral level (33). Regulated GH secretion is essential for optimal linear growth, for homeostasis of carbohydrate, protein, and fat metabolism, and for promoting a positive nitrogen balance (27). These effects are mediated by both insulin-like growth factor I (IGF-I), the downstream effector of GH, and direct effects of the hormone on target tissues.The administration of recombinant porcine GH and GHRH has been extensively studied as a means of enhancing or restoring growth in a variety of mammalian species (4,5,10,21,35). These peptide proteins are degraded in the serum by proteases; therefore either they require relatively frequent dosing or the peptide sequence must be modified to increase its halflife. Under many circumstances, this becomes both time-consuming and expensive. Recently, we demonstrated that plasmid delivery followed by electroporation is an efficient strategy for long-term enhancement of GHRH production (9). Our method of myogenic plasmid delivery requires only a single dose, exerts a longlasting effect on growth, and, because it does not require the use of viral or lipid particles, is advantageous compared with other methods of gene delivery (26).We also have demonstrated that pregnant rat dams treated with this system give birth to pups that have increased nu...