EFFECT OF GROWTH-HORMONE ON THE LOW-LEVEL OF GROWTH-HORMONE BINDING-PROTEIN IN IDIOPATHIC SHORT STATURE

OBJECTIVE Growth hormone receptor status was assessed in children with idiopathic short stature by evaluating plasma growth hormone-binding protein before and under GH therapy. DESIGN Among 22 children presenting idiopathic short stature, 15 were randomly selected to be treated with GH (1.2 IU/kg/week); they were studied before and under GH therapy. Untreated patients served as a control group for age and GH effect. PATIENTS Twenty-two prepubertal children, aged 5-11 years, were studied. They presented growth retardation of -2.8 +/- 0.1 SDS (mean +/- SEM). All had normal GH secretion and their mean IGF-I plasma level was normal. MEASUREMENT Growth hormone-binding protein was measured using high pressure liquid chromatography gel filtration. The specific binding of I-125-hGH to the growth hormone-binding protein was expressed as a percentage of the total radioactivity. RESULTS Specific binding of I-125-hGH to the high affinity growth hormone-binding protein was low with a mean +/- SEM value of 11.1 +/- 0.9% of radioactivity. In the treated group, growth hormone-binding protein increased significantly after 3 months of treatment; it reached 21.1 +/- 1.0% of radioactivity (mean +/- SEM) in the eight children who have been treated for 18 months. In the seven untreated children, the growth hormone-binding protein value increased to 16.2 +/- 1.1% after 18 months; this value is significantly lower than that found in the GH-treated children, demonstrating that the GH effect is greater than the age-related increase in the growth hormone-binding protein. A positive correlation was found between IGF-I plasma levels and growth hormone-binding protein and also between growth velocity and growth hormone-binding protein. CONCLUSIONS The low growth hormone-binding protein and the response to high doses of GH suggest partial GH resistance at the receptor level, in this group of children with idiopathic short stature.