GROWTH-HORMONE INSENSITIVITY SYNDROMES - A PRELIMINARY-REPORT ON CHANGES IN INSULIN-LIKE GROWTH-FACTORS AND THEIR BINDING-PROTEINS DURING TREATMENT WITH RECOMBINANT INSULIN-LIKE GROWTH FACTOR-I

Serum levels of insulin-like growth factor (IGF) binding proteins (IGF BPs) 1, 2 and 3 were studied by radioimmunoassay in 29 patients with g rowth hormone (GH) insensitivity syndromes (GHIS) before and during tr eatment with IGF-1. As in normal subjects, there was a highly signific ant correlation between IGFs and IGFBP-3 but not between IGFs and the other binding proteins, though IGFBP-3 represented only about one-thir d of the total IGFBP concentration. In 6 patients with GH deficiency a nd in 5 patients with GHIS, the pharmacokinetic profile of IGF-I after a single injection was strongly dependent on the IGFBP-3 concentratio n. A slight but significant increase in IGFBP-3 was observed coinciden t with the IGF-I peak, whereas IGFBP-2 increased after a delay of abou t 10 hours. In the patients with GHIS, chronic IGF-I treatment, with t wice-daily injections for 6 months, caused a significant steady declin e of IGF-II and an increase in IGFBP-2, but had no effect on IGFBP-1 a nd IGFBP-3 levels. During IGF-I treatment, an inverse relationship bet ween baseline IGF-I and GH levels was observed. The data suggest that total IGF-I and IGF-II serum levels are determined mainly by IGFBP-3, even in extreme situations such as GHIS, while other IGFBPs are less i mportant. The IGFBP-3 concentration seems to be a major regulator of t he pharmacokinetics of exogenous IGF-I, which, in turn, influences IGF BP-3 levels. This effect of IGF-I on IGFBP-3 is not through induction of IGFBP-3 synthesis, but possibly by reduction of IGFBP-3 clearance. Finally, IGF-I administration suppresses GH secretion.