Author/Editor		Blum, WF; Hall, K; Ranke, MB; Wilton, P; Kržišnik, C
Title		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
Type		članek
Source		Acta Paediatr
Vol. and No.		, št. Suppl 391
Publication year		1993
Volume		str. 15-9
Language		eng
Abstract		Serum levels of insulin-like growth factor (IGF) binding proteins (IGFBPs) 1, 2 and 3 were studied by radioimmunoassay in 29 patients with growth hormone (GH) insensitivity syndromes (GHIS) before and during treatment with IGF-I. As in normal subjects, there was a highly significant correlation between IGFs and IGFBP-3 but not between IGFs and the other binding proteins, though IGFBP-3 represented only about one-third of the total IGFBP concentration. In 6 patients with GH deficiency and in 5 patients with GHIS, the pharmacokinetic profile of IGF-I after a single injection was strongly dependent on the IGFBP-3 concentrations. A slight but significant increase in IGFBP-3 was observed coincident with the IGF-I peak, whereas IGFBP-2 inceased after a delay of about 10 hours. In the patients with GHIS, chronic IGF-I treatment, with twice-daily injections for 6 months, caused a significant steady decline of IGF-II and an increase in IGFBP-2, but had no effect on IGFBP-1 and IGFBP-3 levels. During IGF-I treatment, an inverse relationship between 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 important. The IGFBP-3 concentration seems to be a major regulator of the pharmacokinetics of exogenous IGF-I, which, in turn, influences IGFBP-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.
Descriptors		DWARFISM INSULIN-LIKE GROWTH FACTOR I RECEPTORS, SOMATOTROPIN SOMATOMEDINS ADOLESCENCE ADULT CHILD INSULIN-LIKE GROWTH FACTOR II MODELS, BIOLOGICAL RECOMBINANT PROTEINS SOMATOTROPIN