A minority of patients with
Laron syndrome have normal serum
GH binding protein (GHBP), indicating that the defect is elsewhere than in the extracellular domain of the GH receptor. We have evaluated the effect of long-term
IGF-I treatment on serum
IGF-binding protein (IGFBP)-3 and the
acid-labile subunit (ALS) in three sibling with
Laron syndrome caused by a GH post-receptor defect and with normal GHBP. The children (a boy aged 3 years, a girl aged 4 years and a boy aged 10 years) were treated by daily s.c. injection of
IGF-I in a dose of 150 micrograms/kg.
IGFBP-3 was measured by RIA and Western
ligand blotting, ALS by RIA. Based values of
IGFBP-3 and ALS were low. During
IGF-I treatment, the
IGFBP-3 concentrations in the girl gradually increased, whereas in the boys there was a 60% decrease during the first week, followed by gradual increase towards baseline. The ALS concentrations followed a similar pattern. We conclude that
IGF-I treatment induces and initial suppression and then an increase in the
IGFBP-3 and ALS concentrations, confirming data from animal experiments that
IGFBP-3 synthesis is not solely under GH control. The differences in responsiveness between the female and male siblings may reflect genetic differences, or lower circulating concentrations of
IGF-I in the boys compared with the girl.