LONG-TERM EFFECTS OF INSULIN-LIKE-GROWTH-FACTOR (IGF)-I ON SERUM IGF-I, IGF-BINDING PROTEIN-3 AND ACID-LABILE SUBUNIT IN LARON-SYNDROME PATIENTS WITH NORMAL GROWTH-HORMONE BINDING-PROTEIN

A minority of patients with Laron syndrome have normal serum GH bindin g 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 an d the acid-labile subunit (ALS) in three siblings 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) wer e treated by daily s.c. injection of IGF-I in a dose of 150 mu g/kg. I GFBP-3 was measured by RIA and Western ligand blotting, ALS by RIA. Ba sal values of IGFBP-3 and ALS were low. During IGF-I treatment, the IG FBP-3 concentrations in the girl gradually increased, whereas in the b oys there was a 60% decrease during the first week, followed by gradua l increase towards baseline. The ALS concentrations followed a similar pattern. We conclude that IGF-I treatment induces an initial suppress ion and then an increase in the IGFBP-3 and ALS concentrations, confir ming data from animal experiments that IGFBP-3 synthesis is not solely under GH control. The differences in responsiveness between the femal e and male siblings may reflect genetic differences, or lower circulat ing concentrations of IGF-I in the boys compared with the girl.