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Effect of Chronic Growth Hormone Administration on Skeletal Muscle in Dogs

Merck Sharp & Dolime-Chibret Laboratories, Research Center, Department of Safety Assessment, BP 134, Route de Marsat, 63203 Riom, France

Philippe Laroque

Merck Sharp & Dolime-Chibret Laboratories, Research Center, Department of Safety Assessment, BP 134, Route de Marsat, 63203 Riom, France

Srinivasa Prahalada

Merck Research Laboratories, Department of Safety Assessment, West Point, Pennsylvania 19486, USA

Lea G. Stabinski

Merck Research Laboratories, Department of Safety Assessment, West Point, Pennsylvania 19486, USA

Chao-Min Hoe

Merck Research Laboratories, Department of Biometrics, West Point, Pennsylvania 19486, USA

Chennekatu P. Peter

Merck Research Laboratories, Department of Safety Assessment, West Point, Pennsylvania 19486, USA

Pierre Duprat

Merck Sharp & Dolime-Chibret Laboratories, Research Center, Department of Safety Assessment, BP 134, Route de Marsat, 63203 Riom, France

Matthew J. Van Zwieten

Merck Research Laboratories, Department of Safety Assessment, West Point, Pennsylvania 19486, USA

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 expected 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, Prahalada 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 mass 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 II (fast twitch) myofiber sizes in mid- and high-dose males and in high-dose females. The ratio of type I and type II muscle fibers remained unchanged. Hypertrophic myofibers were enlarged but had a normal histologic and ultrastructural organization 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 an anabolic effect on skeletal muscle in dogs.

Key Words: Muscle hypertrophy • experimental • pharmacological effect • morphometry • electron microscopy

Toxicologic Pathology, Vol. 26, No. 2, 207-212 (1998)
DOI: 10.1177/019262339802600203


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