Effects of Human Growth Hormone Administration on Serum Somatomedins, Somatomedin Carrier Proteins, and Growth Rates in Children with Growth Hormone Deficiency*

Abstract

We have determined the growth rates and serum somatomedin (Sm) and Sm carrier protein (CP) levels in 30 children with GH deficiency and short stature before and up to 3 yr of GH therapy. Initially, the mean (±SEM) bone age (BA) of this group (6.9 ± 0.5 yr) was significantly (Pvs. 1.61 ± 0.12 μg/ml), IGF-I (0.09 ± 0.02 vs. 0.44 ± 0.04/ig/ml), and CP (123 ± 18.8 vs. 366 ± 28.2 μg/ml). Both total IGF and IGF-I were inversely related to the degree of growth retardation, expressed as the ratio of BA to CA. Serum Sm increased in 19 of 21 subjects after short term (up to 18 h) GH administration (0.1 U/kg), but the magnitude of response was not a useful predictor of the Sm response to long term therapy. All subjects exhibited marked increases in growth rate during long term GH therapy (0.1 U/kg, three times weekly), with a mean peak of 11.0 ±0.5 cm/yr during the first 6 months, and 8.4 0.5 cm/yr for the entire period of treatment. Serum total IGF increased from a basal level of 0.31 ± 0.03/μg/ml to a mean of 0.43 ± 0.04/μg/ml (P125I]IGF-I specifically bound to the major chromatographic peaks of serum binding activity in vitro also remained low. However, the quantity of labeled IGF-I bound to the approximately 150,000 molecular weight species increased to normal in response to GH, while that bound to the approximately 60,000 molecular weight form remained unchanged or was even slightly diminished. These studies demonstrate that quantitative relationships exist between GH-induced increments in serum Sm levels and resultant increases in growth rates in GH-deficient children. The data also suggest that other Sms beside IGF-I may be partially GH dependent.