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RESEARCH ARTICLE

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

¹University of Manchester ²Endocrine Sciences Research Group ³University of Sydney ⁴National Institute for Medical Research, UK

Submitted 7 April 2009 ; revised 21 October 2009 ; accepted in final form 22 October 2009

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 if variable GH dose regimens promote growth more effectively than fixed doses. Animals were treated with saline or 4.2mg recombinant bovine GH given as 1) 700µg/week in 100µg/day doses, 2) alternating weekly doses of 966µg (138µg/day) or 434µg (62µg/day) or 3) 700µg/week in randomised daily doses (5-250µg/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 weeks); 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), 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.

GH deficiency; infradian; IGFBP; ALS