Objective: GH deficiency (GHD) causes growth failure and alterations in body composition both in humans and mice. Mouse models of GHD are used to study the effect of GH replacement therapy on these parameters. As the administration of human GH to mice causes development of antibodies and progressive reduction of its effectiveness, the use of species-specific GH is recommended. To determine the optimal GH replacement schedule in GHD mice, and to study its effect on body composition, we treated mice with targeted ablation of the GHRH gene (GHRH knock out-GHRHKO) with recombinant mouse GH (rmGH).
Design: One week-old GHRHKO male animals received either placebo or one of two different regimens of escalating doses of rmGH: R1: 30 microg/daily (1st week), 50 microg/daily (2nd week), 70 microg/daily (3rd-4th week); R2: 15 microg/twice a day (1st week), 25 microg/twice a day (2nd week), 35 microg/twice a day (3rd-4th week). Sex- and age-matched wild-type (WT) animals served as controls. At the end of the study we measured body length and weight, tibia and femur length, and body composition.
Results: While R1 normalized all growth parameters (TBW, N-A, femur, tibia length), R2 mice achieved significantly higher TBW, N-A and femur length when compared to WT. Body composition abnormalities (increased subcutaneous fat and reduced lean mass) were completely reverted by both treatment schedules. None of the GH-induced parameter modification described above was reflected in parallel changes in circulating serum IGF-1 and liver IGF-1 mRNA.
Conclusions: Our findings indicate that in GHD mice body composition changes are reverted by rmGH and that twice/daily is more effective than daily administration.