The effect of different patterns of growth hormone administration on the IGF axis and somatic and skeletal growth of the dwarf rat

Abstract

Normal childhood growth is determined by ultradian and infradian variations in GH secretion, yet GH treatment of children with short stature is restricted to daily fixed doses. We have used GH-deficient dwarf rats to determine whether variable GH dose regimens promote growth more effectively than fixed doses. Animals were treated with saline or 4.2 mg of recombinant bovine GH given as 1) 700 μg/wk in 100 μg/day doses, 2) alternating weekly doses of 966 (138 μg/day) or 434 μg (62 μg/day), or 3) 700 μg/wk in randomized daily doses (5–250 μg/day). Body weight and length were measured weekly. Femur and tibia lengths and internal organ, fat pad, and muscle weights were recorded at the end of the study (6 wk); blood was collected for IGF axis measurements. GH promoted femur [ F(3,60) = 14.67, P < 0.05], tibia [ F(3,60) = 14.90, P < 0.05], muscle [ F(3,60) = 10.37, P < 0.05], and organ growth [liver: F(3,60) = 9.30, P < 0.05; kidney: F(3,60) = 2.82, P < 0.05] and an increase in serum IGF-I [ F(3,60) = 9.18, P < 0.05] and IGFBP-3 [ F(3,60) = 6.70, P < 0.05] levels. IGF-I levels correlated with final weight ( r = 0.45, P < 0.05) and length ( r = 0.284, P < 0.05) in the whole cohort, but within each group, growth parameters correlated with serum IGF-I only in animals treated with random GH doses. The variable regimens promoted femur length ( P < 0.05) and muscle ( P < 0.05) and kidney ( P < 0.05) weight more effectively than treatment with the fixed regimen. This study demonstrates that aspects of growth are improved following introduction of infradian variation to GH treatment in a GH-deficient model. The data suggest that varying the pattern of GH doses administered to children may enhance growth performance without increasing the overall GH dose.