Effect of Chronic Growth Hormone Administration on Skeletal Muscle in Dogs

Abstract

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.

Morphological Changes in the Kidney of Dogs Chronically Exposed to Exogenous Growth Hormone

“…The glomeruli from control dogs had normal ultrastructural features ( Figure 4) consistent with published data (47 (17,34,37,44 70-fold greater in the low-, mid-, and high-dose groups, respectively, than in the control group. The mean serum IGF-1 levels, expressed as systemic exposure (AUCI-1h), in the mid-and high-dose groups were 3-to 5-fold greater than in the control group.…”

“…Pharmacological and toxicological effects of chronic administration of GH to beagle dogs have been described in detail (34,37,44). Anabolic and catabolic effects of elevated serum GH and IGF-1 resulting from porcine growth hormone (pGH) administration on biochemical and morphological parameters (44) as well as on skeletal muscle (37) and pituitary (34) have been described. pGH was selected for the above study because of its known structural identity to canine GH (1) (44).…”

Capromorelin increases food consumption, body weight, growth hormone, and sustained insulin‐like growth factor 1 concentrations when administered to healthy adult Beagle dogs

“…We hypothesize that the increase in serum GH and IGF‐1 demonstrated in this study may result in positive effects on lean muscle mass over a longer‐term treatment, as has been shown in dogs treated with GH (Molon‐Noblot et al ., ). To demonstrate the hypothesized effect on body composition, a study using advanced imaging techniques to assess the effects of capromorelin on lean body mass and body fat would be necessary.…”

Musculoskeletal System

“…341 Acromegaly is a well-known condition associated with a widespread increase in visceral size including an increase in muscle mass. 343 Whether growth hormone mediates this effect directly on skeletal muscle remains unclear but there is now considerable evidence that somatomedins or insulin-like growth factors are capable of mediating the effects of growth hormone on muscle. 342 A similar increase in type I fibers has also been reported in beagle dogs dosed with porcine growth hormone chronically by the subcutaneous route.…”