Effect of chronic growth hormone administration on skeletal muscle in dogs. Toxicol

Administration of growth hormone (GH) results in increased body weight gain in dogs. Increased body weight gain is believed to be a result of the trophic effect of GH on the musculoskeletal system. However. edema is one of the side effects described in man following exogenous GH administration. Thus, the objective of this study was to determine if the expectcd increased weight gain in GH-treated dogs is a result of increased muscle mass. Porcine growth hormone (pGH). administered subcutaneously to beagle dogs at doses of 0.025, 0.1, and 1 IU/kg/day for 14 wk, resulted in elevated serum GH and insulin-like growth factor-1 (IGF-1) levels (see accompanying paper, Pnhalada et al). This was associated with a significant increase in body weight gain and weights of the cranial tibialis muscle in both male and female dogs. The increased muscle m+ss likely contributed to the significant increase in body weight gain seen in both sexes. Quantitative analysis of skeletal muscle sections stained for ATPase activity showed increases in type I (slow twitch) and type I1 (fast twitch) myofiber sizes in mid- and high-dose males and in high-dose females. The ratio of type I and type I1 muscle fibers remained unchanged. Hypertrophic myofibers were enlarged but had a normal histologic and ultrastructural organi-zation when observed by light and transmission electron microscopy. The results of this study have demonstrated that increased muscle mass in pGH-treated dogs is related to hypertrophy of muscle fibers and not due to edema. Exogenous GH administration has a