Effects of recombinant mouse growth hormone treatment on growth and body composition in GHRH knock out mice.
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).


METHODS
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.
Alba
Maria
M
Department of Medicine, Division of Endocrinology, and the Ilyssa Center for Molecular and Cellular Endocrinology, Johns Hopkins University School of Medicine, 1830 East Monument Street #333, Baltimore, MD 21287, USA.
Fintini
Danilo
D
Salvatori
Roberto
R
D000818:Animals; D001823:Body Composition / Q000187:drug effects*; D049628:Body Size; D001835:Body Weight / Q000187:drug effects*; D013006:Growth Hormone / Q000008:administration & dosage*; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone