Endocrine Abstracts

Good growth in children is associated with large, disordered, fluctuations in GH levels from week to week (Gill et al., 1999; Gill et al., 2001). However, GH treatment regimens are restricted to daily fixed doses which may not provide optimal growth. We have used GH-deficient dwarf rats (dw/dw) to test our hypothesis that variable GH dosing will enhance growth.

Six week old, male dwarf rats (16 per group) were treated for 6 weeks with either saline or recombinant bovine GH (rbGH) given in one of 3 treatment regimens: a) a fixed daily dose of 100 μg, b) a high/low dose schedule (62 μg/d and 138 μg/d alternating weekly) or c) a daily dose between 5 and 250 μg/d randomised within each week to provide a total of 700 μg/week. Weight was measured thrice weekly and body length weekly. Animals were sacrificed after 6 weeks, organs weighed and tibia and femur lengths measured.

After 1 week, all GH treated groups showed improved growth with regard to both length (P=0.001) and weight (P=0.002) compared to controls. After 6 weeks, only animals given a random dose showed significant enhancement of total body length (P=0.047) or weight gain (P=0.025) compared to controls.

At 6 weeks, both tibial length (P=0.001) and width (P=0.007) were significantly enhanced in group c whilst femur length was significantly enhanced in both groups b (P=0.003) and c (P=0.005).

No significant differences were detected in heart or fat weights between treatment groups. However, the weights of lungs (−ve; P=0.001), muscles (+ve; P=0.001), livers (+ve; P=0.022), and kidneys (+ve; P=0.048) showed significant treatment dependent variation with groups b and c being most efficacious.

We demonstrate that a random dosing regimen has more potent anabolic effects on weight, long bone growth and GH-sensitive organ weight than fixed daily doses. This suggests that a random GH dosing regimen may improve children’s growth performance for the same overall GH dose.